Genes associated with progression and response in chronic myeloid leukemia and uses thereof

ABSTRACT

The invention provides molecular markers that are associated with the progression of chronic myeloid leukemia (CML), and methods and computer systems for monitoring the progression of CML in a patient based on measurements of these molecular markers. The present invention also provides CML target genes, and methods and compositions for treating CML patients by modulating the expression or activity of these CML target genes and/or their encoded proteins. The invention also provides genes that are associated with resistance to imatinib mesylate (Gleevec™) treatment in CML patients, and methods and compositions for determining the responsiveness of a CML patient to imatinib mesylate treatment based on measurements of these genes and/or their encoded proteins. The invention also provides methods and compositions for enhancing the effect of Gleevec™ by modulating the expression or activity of these genes and/or their encoded proteins.

This application claims the benefit, under 35 U.S.C. §19(e), of U.S. Provisional Patent Application No. 60/751,455, filed on Dec. 15, 2005, which is incorporated herein by reference in its entirety.

This invention was made with U.S. Government support under Contract Nos. CA-18029 and CA-85053 awarded by the National Institutes of Health of the United States Department of Health and Human Services. The U.S. Government has certain rights in the invention.

This application includes a Sequence Listing submitted on compact disc, recorded on two compact discs, including one duplicate, containing Filename seqlisting 9301-253-999 as filed.txt, of size 10,385,215 bytes, created Dec. 8, 2006. The Sequence Listing on the compact discs is incorporated by reference herein in its entirety.

1. FIELD OF THE INVENTION

The invention relates to molecular markers that are associated with the progression of chronic myeloid leukemia (CML). The invention also relates to methods and computer systems tor evaluating the progression of CML based on these molecular markers. The present invention also relates to methods and compositions for treating CML patients by modulating the expression or activity of certain genes involved in CML progression and/or their encoded proteins. The invention further relates to methods and compositions for determining the responsiveness of a CML patient to imatinib mesylate (Gleevec™).

2. BACKGROUND OF THE INVENTION

Chronic myeloid leukemia (CML) is a hematopoetic stem cell disease with distinct biological and clinical features. In humans, a majority of CML (about 95%) has been found to be associated with a chromosomal abnormality that involves a t(9;22)(q34;q11) translocation, which results in the expression of the BCR/ABL fusion gene (Philadelphia Chromosome or Ph). The rest is associated with either a cryptic translocation that is invisible on G-banded chromosome preparations or a variant translocation involving another chromosome or chromosomes as well as chromosomes 9 and 22. CML usually presents in the so-called chronic phase, in which the clonal expansion of mature myeloid cells leads to an elevated white blood cell (WBC) count. Without curative intervention chronic phase CML will invariably transform through a phase of “acceleration,” often heralded by the appearance of increased immature myeloid cells in the bone marrow and peripheral blood, as well as new cytogenetic changes in addition to the Ph chromosome. Progression then proceeds quickly to blast crisis, with immature blast cells overwhelming the production of normal hematopoetic elements. Blast crisis is highly resistant to treatment, with death generally occurring from infection and bleeding complications secondary to the absence of normal granulocytes and platelets. The median time from diagnosis of chronic phase CML to progression blast crisis is approximately 3-4 years but the range of timing is quite broad, encompassing from 0.5-15 years (Faderl et al., 1999, Ann Intern Med 131:207).

There is a broad range of treatment options for CML. All treatments work far better on chronic phase disease than on accelerated or blast phase. The only known curative therapy for CML is stem cell transplantation, a complex and potentially toxic modality that carries a high potential for morbidity and mortality (Radich et al., 2003, Blood 102:31). Non-transplant therapy includes alpha interferon, which can produce a major reduction in the proportion of Ph positive cells and extend the natural history of the disease in approximately 10-20% of cases (Kantarjian et al., 1999, J Clin Oncol 17:284). The tyrosine kinase inhibitor, imatinib mesylate, suppresses the Ph to the point where it is undetectable by cytogenetic evaluation (“complete cytogenetic remission”) in >70% of newly diagnosed chronic phase CML cases (Druker et al., 2001, N Engl J Med 344:1031). The duration of such responses is unknown, as is potential for cure with imatinib. Resistance to imatinib occurs (especially in advanced phase disease) often accompanied by point mutations in the active area of imatinib binding in the abl gene (Shah et al., 2002, Cancer Cell 2:117). The natural history of such relapses is unknown, though some appear to have a speedy entry into advanced disease (Branford et al., 2003, Blood 102:276).

U.S. Patent Application Publication No. 2003/0104426 A1 discloses genetic markers whose expression correlates with progression of CML. Specifically, the patent application discloses sets of markers whose expression patterns can be used to differentiate chronic phase individuals from those in blast crisis, and methods of using these markers to distinguish these conditions. The patent application also discloses kits containing ready-to-use microarrays and computer data analysis software for carrying out the disclosed methods.

PRAME (Preferentially Expressed Antigen of Melanoma) was identified as a tumor antigen recognized by cytotoxic T-cells against a melanoma surface antigen (Matsushita et al., 2001, Br J Haematol 112:916, 2001; van Baren et al., 1998, Br J Haematol 102:1376). PRAME has been found to be overexpressed in over 25% of leukemia, and has been found to be induced by Bcr-Abl in CML cell lines (Watari et al., 2000, FEBS Lett 466:367). PRAME over-expression has been described as one of the few features that characterize the transient myeloproliferative syndrome of Down's syndrome from the progressive acute megakaryoblastic leukemia found in that disorder (McElwaine et al., 2004, Br J Haematol 125:729).

The genetic events that cause the progression of chronic phase to blast crisis CML are unknown (Calabretta et al., 2004, Blood 103:4010; Shet et al., 2002, Leukemia 16:1402). Numerous genetic abnormalities have been demonstrated, including chromosomal changes including a multiplication of the Ph, the disruption of TP53, the deletion of the p15/p16 tumor suppressor genes (the latter only in lymphoid blast crisis). However, none of these changes are particularly common. Genetic instability is apparent in the additional chromosomal changes that occur with progression, though standard assays of instability, such as alterations in minisatellite repeats, is relatively uncommon (Wada et al., 1994, Blood 83:3449; Mori et al., 1997, Leukemia 11:151). Unfortunately, clinical and molecular tests cannot predict where on the “clock” of progression an individual lies at the time of the initial diagnosis, and this makes it impossible to tailor therapy to the degree of risk that faces an individual CML patient. It is also not possible to identify the subset of patients who will benefit most from the variety of therapy options, such as interferon, imatinib, or transplantation. Thus, presently tailoring therapy to individual risk is difficult. There is therefore a need to identify genes whose levels of expression change during the evolution of the chronic phase to blast crisis. There is a need for methods that utilize measured expression levels of such genes to determine the phase and/or progression of CML in a patient. There is also a need for methods of treating CML by targeting such genes.

Discussion or citation of a reference herein shall not be construed as an admission that such reference is prior art to the present invention.

3. SUMMARY OF THE INVENTION

The invention provides a method for determining the progression of chronic myeloid leukemia (CML) in a patient, comprising (a) classifying a marker profile comprising measurements of a plurality of gene products in a cell sample taken from said patient as a chronic phase (CP-CML) profile or as an advanced phase (ADV-CML) profile, wherein said gene products are respectively products of at least 5 of the genes listed in Table 1a and/or Table 1b or respective functional equivalents thereof, wherein at least one of said 5 genes is from Table 1a; and (b) determining said patient as in a chronic phase if said marker profile is classified as a CP-CML profile, or determining said patient as in an advanced phase if said marker profile is classified as an ADV-CML profile. In one embodiment, said plurality of gene products are of at least 5, 10, 20, 50, 70 or 100 of the genes listed in Table 1a. In one embodiment, said cell sample is a bone marrow sample or a peripheral blood sample.

In one embodiment, the method further comprises obtaining said marker profile by a method comprising measuring said plurality of gene products in a cell sample taken from said patient.

In preferred embodiments, said gene products are products of at least 10, at least 20, at least 40, at least 70, at least 100, or at least 500 of the genes, respectively, listed in Table 1a and/or 1b.

In another preferred embodiment, said gene products are products of at least 10, at least 20, at least 40, at least 70, at least 100, or at least 200 of the genes, respectively, listed in Table 2a.

In still another preferred embodiment, said gene products are products of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or all of the genes, respectively, corresponding to the markers listed in Table 3. In one embodiment, said gene products are products of at least 5, 6, 7, 8, 9 or all of the genes, respectively, corresponding to the up-regulated markers listed in Table 3, or are products of at least 5, 6, 7, 8, 9 or all of the genes, respectively, corresponding to the down-regulated markers listed in Table 3.

In one embodiment, each of said gene products is a gene transcript.

In one embodiment, measurement of each said gene transcript is obtained by a method comprising contacting a positionally-addressable microarray with nucleic acids from said cell sample or nucleic acids derived therefrom under hybridization conditions, and detecting the amount of hybridization that occurs, said microarray comprising one or more polynucleotide probes complementary to a hybridizable sequence of each said gene transcript.

In another embodiment, measurement of each said gene transcript is obtained by quantitative reverse transcriptase PCR (qRT-PCR).

In another embodiment, each of said plurality of gene products is a protein.

In a preferred embodiment, said classifying is carried out using a progression classifier, which receives an input comprising said marker profile and provides an output comprising data indicating whether said marker profile is a CP-CML profile or an ADV-CML profile.

In one embodiment, said progression classifier is trained with training data from a plurality of training CML patients, wherein said training data comprise for each of said plurality of training CML patients (i) a training maker profile comprising measurements of said plurality of gene products in a cell sample taken from said training patient; and (ii) data indicating whether said training patient is in CP-CML or ADV-CML.

In a preferred embodiment, said progression classifier comprises a CP-CML template comprising measurements of said plurality of gene products representative of measurements of said plurality of genes products in a plurality of patients having CP-CML and/or an ADV-CML template comprising measurements of said plurality of gene products representative of measurements of said plurality of genes products in a plurality of patients having ADV-CML, and said step of classifying is carried out by a method comprising (i) comparing said marker profile with said CP-CML template and/or said ADV-CML template; and (ii) classifying said marker profile as a CP-CML profile if said marker profile has a high similarity to said CP-CML template and/or has a low similarity to said ADV-CML template, or classifying said marker profile as a ADV-CML profile if said marker profile has a high similarity to said ADV-CML template and/or has a low similarity to said CP-CML template, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.

In a specific embodiment, said step of classifying is carried out by a method comprising (i) comparing said marker profile with said CP-CML template or said ADV-CML template; and (ii) classifying said marker profile as a CP-CML profile if said marker profile has a high similarity to said CP-CML template or has a low similarity to said ADV-CML template, or classifying said marker profile as a ADV-CML profile if said marker profile has a high similarity to said ADV-CML template or has a low similarity to said CP-CML template, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.

In another specific embodiment, said step of classifying is carried out by a method comprising (i) comparing said marker profile with said CP-CML template and said ADV-CML template; and (ii) classifying said marker profile as a CP-CML profile if said marker profile has a higher similarity to said CP-CML template than to said ADV-CML template, or classifying said marker profile as a ADV-CML profile if said marker profile has a higher similarity to said ADV-CML template than to said CP-CML template.

In one embodiment, said similarity to said CP-CML template is represented by a correlation coefficient between said marker profile and said CP-CML template, wherein said similarity to said ADV-CML template is represented by a correlation coefficient between said marker profile and said ADV-CML template. In one embodiment, said correlation coefficients between said marker profile and said CP-CML template and said ADV-CML template are respectively calculated according to the equation P _(i)=({right arrow over (z)} _(i) ·{right arrow over (y)})/(∥{right arrow over (z)} _(i) ∥·∥{right arrow over (y)}∥) where i=1 and 2, wherein {right arrow over (y)} represents said marker profile, {right arrow over (z)}₁ represents said CP-CML template, and {right arrow over (z)}₂ represents said ADV-CML template, P₁ represents said correlation coefficient between said marker profile and said CP-CML template, and P₂ represents said correlation coefficient between said marker profile and said ADV-CML template.

In one embodiment, the measurement of each gene product in said CP-CML template or said ADV-CML template is an average of the measurements of said gene product in a plurality of CP-CML patients or in a plurality of ADV-CML patients, respectively.

In one embodiment, said measurement of each gene product in said marker profile is a relative level of said gene product in said cell sample taken from the patient versus level of said gene product in a reference pool, represented as a log ratio; the respective measurement of each gene product in said CP-CML template is a relative level of said gene product representative of level of said gene product in a plurality of CP-CML patients versus level of said gene product in a reference pool, represented as a log ratio; and the respective measurement of each gene product in said ADV-CML template is a relative level of said gene product representative of level of said gene product in a plurality of ADV-CML patients versus level of said gene product in a reference pool, represented as a log ratio.

In one embodiment, the respective log ratio for each gene product in said CP-CML template or said ADV-CML template is an average of the log ratios for said gene product in a plurality of CP-CML patients or in a plurality of ADV-CML patients, respectively.

In another preferred embodiment, said progression classifier is an artificial neural network (ANN) or a support vector machine (SVM).

The invention also provides a method for assigning a therapeutic regimen for a CML patient, comprising (a) determining the progression of said patient using any of the above described methods; and (b) assigning said patient a therapeutic regimen according to the status of progression determined in step (a). In one embodiment, said patient is determined to be in ADV-CML, and said therapeutic regimen assigned to said patient comprises bone marrow transplant.

The invention also provides a method for enrolling CML patients for a clinical trial of an agent for treating CML, comprising (a) determining the progression of said patient using any of the above described methods; and (b) assigning each patient having a CP-CML to one patient group and each patient having an ADV-CML to another patient group, at least one of said patient group being enrolled in said clinical trial.

The invention also provides a method for determining the responsiveness of a chronic myeloid leukemia (CML) patient to imatinib mesylate (IM), comprising (a) determining the progression of said patient using any of the above described methods; and (b) determining said patient as responsive to IM treatment if said marker profile is classified as a CP-CML profile, or determining said patient as resistant to IM treatment if said marker profile is classified as an ADV-CML profile.

In another aspect, the invention provides a method for determining the responsiveness of a chronic myeloid leukemia (CML) patient to imatinib mesylate (IM), comprising (a) classifying a marker profile comprising measurements of a plurality of gene products in a cell sample taken from said patient as an IM-sensitive profile or an IM-resistant profile, wherein said gene products are respectively products of at least 5 of the genes listed in Table 4 or respective functional equivalents thereof, and (b) determining said patient as responsive to IM treatment if said marker profile is classified as an IM-sensitive profile, or determining said patient as resistant to IM treatment if said marker profile is classified as an IM-resistant profile. In one embodiment, said plurality of gene products are of at least 5 of the genes listed in Table 4. In one embodiment, said cell sample is a bone marrow sample or a peripheral blood sample.

In one embodiment, the method further comprises obtaining said marker profile by a method comprising measuring said plurality of gene products in a cell sample taken from said patient.

In preferred embodiments, said gene products are products of at least 10, at least 20, at least 40, at least 70, at least 100, or at least 200 of the genes, respectively, listed in Table 4.

In one embodiment, each of said gene products is a gene transcript.

In one embodiment, measurement of each said gene transcript is obtained by a method comprising contacting a positionally-addressable microarray with nucleic acids from said cell sample or nucleic acids derived therefrom under hybridization conditions, and detecting the amount of hybridization that occurs, said microarray comprising one or more polynucleotide probes complementary to a hybridizable sequence of each said gene transcript.

In another embodiment, each of said plurality of gene products is a protein.

In a preferred embodiment, said classifying is carried out by a method comprising using a progression classifier, wherein said progression classifier receives an input comprising said marker profile and provides an output comprising data indicating whether said marker profile is an IM-sensitive profile or an IM-resistant profile.

In one embodiment, said progression classifier is trained with training data from a plurality of training CML patients, wherein said training data comprise for each of said plurality of training CML patients (i) a training maker profile comprising measurements of said plurality of gene products in a cell sample taken from said training patient; and (ii) data indicating whether said training patient is sensitive or resistant to imatinib mesylate.

In one embodiment, said progression classifier comprises an IM-sensitive template comprising measurements of said plurality of gene products representative of measurements of said plurality of genes products in a plurality of patients responsive to IM treatment and/or an IM-resistant template comprising measurements of said plurality of gene products representative of measurements of said plurality of genes products in a plurality of patients resistant to IM treatment, and said step of classifying is carried out by a method comprising (a1) comparing said marker profile with said IM-sensitive template and/or said IM-resistant template; and (a2) classifying said marker profile as a IM-sensitive profile if said marker profile has a high similarity to said IM-sensitive template and/or has a low similarity to said IM-resistant template, or classifying said marker profile as a IM-resistant profile if said marker profile has a high similarity to said IM-resistant template and/or has a low similarity to said IM-sensitive template, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.

In a specific embodiment, said step of classifying is carried out by a method comprising (a1) comparing said marker profile with said IM-sensitive template or said IM-resistant template; and (a2) classifying said marker profile as an IM-sensitive profile if said marker profile has a high similarity to said IM-sensitive template or has a low similarity to said IM-resistant template, or classifying said marker profile as a IM-resistant profile if said marker profile has a high similarity to said IM-resistant template or has a low similarity to said IM-sensitive template, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.

In another specific embodiment, said step of classifying is carried out by a method comprising (a1) comparing said marker profile with said IM-sensitive template and said IM-resistant template; and (a2) classifying said marker profile as an IM-sensitive profile if said marker profile has a higher similarity to said IM-sensitive template than to said IM-resistant template, or classifying said marker profile as a IM-resistant profile if said marker profile has a higher similarity to said IM-resistant template than to said IM-sensitive template.

In one embodiment, said similarity to said IM-sensitive template is represented by a correlation coefficient between said marker profile and said IM-sensitive template, and said similarity to said IM-resistant template is represented by a correlation coefficient between said marker profile and said IM-resistant template.

In one embodiment, said correlation coefficients between said marker profile and said IM-sensitive template and said IM-sensitive template are respectively calculated according to the equation P _(i)=({right arrow over (z)} _(i) ·{right arrow over (y)})/(∥{right arrow over (z)} _(i) ∥·∥{right arrow over (y)}∥) where i=1 and 2, wherein {right arrow over (y)} represents said marker profile, {right arrow over (z)}₁ represents said IM-sensitive template, and {right arrow over (z)}₂ represents said IM-resistant template, P₁ represents said correlation coefficient between said marker profile and said IM-sensitive template, and P₂ represents said correlation coefficient between said marker profile and said IM-resistant template.

In one embodiment, the measurement of each gene product in said IM-sensitive template or said IM-resistant template is an average of the measurements of said gene product in a plurality of patients responsive to IM treatment or in a plurality of patients resistant to IM treatment, respectively.

In one embodiment, said measurement of each gene product in said marker profile is a relative level of said gene product in said cell sample taken from the patient versus level of said gene product in a reference pool, represented as a log ratio; the respective measurement of each gene product in said IM-sensitive template is a relative level of said gene product representative of level of said gene product in a plurality of patients responsive to IM treatment versus level of said gene product in a reference pool, represented as a log ratio; and the respective measurement of each gene product in said IM-resistant template is a relative level of said gene product representative of level of said gene product in a plurality of patients resistant to IM treatment versus level of said gene product in a reference pool, represented as a log ratio.

In one embodiment, the respective log ratio for each gene product in said IM-sensitive template or said IM-resistant template is an average of the log ratios for said gene product in a plurality of patients responsive to IM treatment or in a plurality of ADV-CML patients, respectively.

In another preferred embodiment, said progression classifier is an artificial neural network (ANN) or a support vector machine (SVM).

The invention also provides a method for assigning a treatment regimen for a CML patient, comprising (i) determining whether said patient is responsive or resistant to imatinib mesylate using a method as described above; and (ii) assigning said patient a treatment regimen comprising bone marrow transplant if said patient is determined to be resistant to imatinib mesylate.

The invention also provides a method for enrolling CML patients for a clinical trial of a treatment modality for treating CML, comprising (i) determining whether said patient is responsive or resistant to imatinib mesylate using a method as described above; and (ii) assigning each patient who is predicted to be resistant to imatinib mesylate to one patient group and each patient who is predicted to be responsive to imatinib mesylate to another patient group, at least one of said patient group being enrolled in said clinical trial.

In still another aspect, the invention provides a method for treating a patient having chronic myeloid leukemia (CML), comprising administering to said patient a treatment regimen, said treatment regimen comprising one or more agents that modulate the expression and/or activity of one or more different genes listed in one or more of Tables 2a, 2b, 5a and 5b and/or their encoded proteins, wherein said patient exhibits aberrant regulation of said one or more genes.

In one embodiment, said one or more different genes are selected from the different genes listed in one or more of Tables 2a and 5a.

In another embodiment, said one or more different genes are selected from the genes listed in both Tables 2a and 5a, i.e., genes common in Tables 2a and 5a.

In still another embodiment, said one or more different genes are selected from the genes listed in Table 3.

In one embodiment, said one or more different genes are selected from the up-regulated genes listed in Table 3, and said treatment regimen comprises a substance selected from the group consisting of siRNA, antisense nucleic acid, ribozyme, and triple helix forming nucleic acid, each reducing the expression of one or more of said one or more different genes in said patient.

In another embodiment, said one or more different genes are selected from the up-regulated genes listed in Table 3, and said treatment regimen comprises a substance selected from the group consisting of antibody, peptide, and small molecule, each reducing the activity of one or more of proteins encoded by said one or more different genes in said patient.

In a preferred embodiment, said treatment regimen comprises an siRNA targeting said one or more different genes.

In preferred embodiment, said one or more different genes consisting of 2, 3, 4, 5, 6, or 10 different genes.

In another embodiment, said one or more different genes are selected from the down-regulated genes listed in Table 3, and said treatment regimen comprises subjecting said patient to gene therapy, said gene therapy enhancing the expression of said one or more different genes in said patient.

In one embodiment, the methods of the invention further comprises determining a transcript level of each of said one or more different genes, and said patient is determined to exhibit aberrant regulation of said different gene if said transcript level deviated from a predetermined threshold level. In some embodiments, said transcript level deviates from said predetermined threshold level by at least 1.5-fold, 2-fold or 3-fold.

In one embodiment, each said transcript level is determined by a method comprising measuring the transcript level of said different gene using one or more polynucleotide probes, each of said one or more polynucleotide probes comprising a nucleotide sequence complementary to a hybridizable sequence in said transcript of said different gene. In one embodiment, said one or more polynucleotide probes are polynucleotide probes on a microarray.

In another embodiment, each said transcript level is determined by a method comprising measuring the transcript level of said different gene using quantitative reverse transcriptase PCT (qRT-PCR).

In still another aspect, the invention provides a method for treating a patient having chronic myeloid leukemia (CML), comprising administering to said patient a treatment regimen, said treatment regimen comprising (i) an effective amount of imatinib mesylate (IM), and (ii) an agent other than IM, wherein said agent modulates the expression and/or activity of 1, 2, 3, 4, 5, 10 or more of the genes listed in Table 4 and/or their encoded proteins, and wherein said patient exhibits aberrant regulation of said one or more genes.

In one embodiment, said one or more genes are selected from the group consisting of the up-regulated genes listed in Table 4, and said agent comprises a substance selected from the group consisting of siRNA, antisense nucleic acid, ribozyme, and triple helix forming nucleic acid, each reducing the expression of one or more of said one or more genes in said patient.

In another embodiment, said one or more genes are selected from the group consisting of the up-regulated genes listed in Table 4, and said agent comprises a substance selected from the group consisting of antibody, peptide, and small molecule, each reducing the activity of one or more of proteins encoded by said one or more genes in said patient.

In one embodiment, said treatment regimen comprises an siRNA targeting said one or more target genes.

In some embodiments, said one or more genes consists of at least 2, 3, 4, 5, 6, or 10 target genes.

In one embodiment, said one or more genes are selected from the group consisting of the down-regulated genes listed in Table 4, and said agent comprises subject said patient to gene therapy, said gene therapy enhancing the expression of said one or more genes in said patient.

The methods can further comprises determining a transcript level of each said gene, and said patient is determined to exhibit aberrant regulation of said gene if said transcript level deviated from a predetermined threshold level. In some embodiment, said transcript level deviates from said predetermined threshold level by at least 1.5-fold, 2-fold or 3-fold.

In one embodiment, each said transcript level is determined by a method comprising measuring the transcript level of said gene using one or more polynucleotide probes, each of said one or more polynucleotide probes comprising a nucleotide sequence complementary to a hybridizable sequence in said transcript of said different gene.

In one embodiment, said one or more polynucleotide probes are polynucleotide probes on a microarray.

In another embodiment, each said transcript level is determined by a method comprising measuring the transcript level of said CML target gene using quantitative reverse transcriptase PCT (qRT-PCR).

In still another aspect, the invention provides a method for diagnosing whether a patient has advanced phase chronic myeloid leukemia (CML), comprising (a) contacting cells a cell sample from said patient with an antibody conjugate, said antibody conjugate comprising an antibody that binds a PRAME protein, said antibody being conjugated with a label; and (b) detecting said label on said cells, wherein detection of said label above a predetermined threshold indicates that said patient has advanced phase CML. The cell sample can be a bone marrow sample or a peripheral blood sample.

In one embodiment, said antibody is a monoclonal antibody.

In another embodiment, said label is fluorescence label, and said detecting is carried out using a fluorescence activated cell sorter.

In still another aspect, the invention provides a method for treating a patient having chronic myeloid leukemia (CML), comprising administering to said patient a therapeutically sufficient amount of an antibody, wherein said antibody binds a PRAME protein, and wherein said patient expresses PRAME protein on hematopoetic stem cells and/or immature myeloid cells. The invention also provides a method for treating a patient having chronic myeloid leukemia (CML), comprising administering to said patient a therapeutically sufficient amount of an antibody conjugate comprising an antibody that binds a PRAME protein, said antibody being conjugated with a therapeutic molecule, wherein said patient expresses PRAME protein on hematopoetic stem cells and/or immature myeloid cells.

In one embodiment, said antibody is a monoclonal antibody.

The invention also provides a method for ex vivo depletion of advanced phase hematopoetic stem cells and/or immature myeloid cells from a bone marrow or peripheral blood sample of a patient, comprising (a) incubating said bone marrow or peripheral blood sample with an antibody that binds a PRAME protein; and (b) removing cells having said antibody attached. The invention also provides a method for treating a patient having chronic myeloid leukemia (CML), comprising (i) depleting advanced phase hematopoetic stem cells and/or immature myeloid cells from a bone marrow or peripheral blood sample of said patient using the method described above; and (ii) transplanting the sample obtained in step (i) to said patient.

In still another aspect, the invention provides a method for identifying a set of genes that are associated with progression of chronic myeloid leukemia (CML), comprising: (a) subtracting from each of a plurality of CML expression profiles a CD34+ expression profile to obtain a plurality of CD34+(−) CML expression profiles, each said CML expression profile comprising levels of expression of a plurality of genes in cells of one of a plurality of chronic myeloid leukemia (CML) patients, said CD34+ expression profile comprising levels of expression of said plurality of genes in non cancerous immature CD34+ cells, said plurality of CML patients comprising patients of different phases of CML; (b) comparing said plurality of CD34+(−) CML expression profiles; and (c) identifying one or more genes that exhibit significant differences in levels of expression between different phases of CML across said plurality of CD34+(−) CML expression profiles.

In one embodiment, said comparing is carried out by ANOVA and said identifying is carried out by identifying one or more genes one or more genes whose p-value corresponds to a predetermined significance level. In one embodiment, said predetermined significance level is p<10⁻⁸.

The method can further comprise: (d) comparing levels of expression of said identified genes between cells of CML blast crisis and normal immature CD34+ cells; and (e) selecting those genes that exhibit significant differences in expression.

In another embodiment, said comparing is carried out by ANOVA and said selecting is carried out by selecting one or more genes whose p-value corresponds to a predetermined significance level. In one embodiment, said predetermined significance level is p-value<0.01%.

The invention also provides a computer system comprising a processor, and a memory coupled to said processor and encoding one or more programs, wherein said one or more programs cause the processor to carry out any one of the methods of the invention.

The invention also provides a computer program product for use in conjunction with a computer having a processor and a memory connected to the processor, said computer program product comprising a computer readable storage medium having a computer program mechanism encoded thereon, wherein said computer program mechanism may be loaded into the memory of said computer and cause said computer to carry out any one of the methods of the invention.

In still anther aspect, the invention provides a microarray comprising for each of a plurality of genes, said genes being at least 5 of the genes selected from the group consisting of the genes as identified respectively by SEQ ID NOS: 1-3968, wherein at least one of said 5 genes is not a gene selected from the group consisting of genes as identified respectively by SEQ ID NOS: 56, 65, 70, 177, 190, 199, 1758, 1773, 1774, 1776, 1786, 1815, 1823, 3925, 3933, 3947, 3956, and 3961, one or more polynucleotide probes complementary and hybridizable to a sequence in said gene, wherein polynucleotide probes complementary and hybridizable to said genes constitute at least 50%, 70%, 80%, 90% or 98% of the probes on said microarray.

In one embodiment, said plurality of genes is at least 10, 20, 40, 70, 100, or 200 genes.

In another embodiment, said plurality of genes is selected from the group consisting of the genes listed in Tables 1a and/or 1b.

In still another embodiment, said plurality of genes is selected from the group consisting of the genes listed in Tables 2a and/or 2b.

In still another embodiment, said plurality of genes is at least 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or all 20 of the genes listed in Table 3.

In still another embodiment, said plurality of genes are selected from the group consisting of the genes listed in Table 4.

In still another embodiment, said plurality of genes is selected from the group consisting of the genes listed in Tables 5a and/or 5b.

4. BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1. Genes associated with CML progression. Samples of CML cases in chronic phase, accelerated by cytogenetic criteria only, accelerated phase, blast crisis, and blast crisis “in remission” were compared to a pool of chronic phase RNA. Approximately 3,000 genes were significantly associated with progressive disease at a significance level of p<10⁻¹¹. Each row represents one sample, and each column represents one gene. A darker color indicates over-expression relative to the control pool, and a lighter color indicates low-expression.

FIG. 2. 2 a: Genes differentially expressed in blast crisis CML compared to normal CD34+ stem cells. CML blast crisis samples with >70% blasts were compared to normal CD34+ bone marrow stem cells. 2 b: Approximately 400 genes were significantly differentially expressed between CML blasts and their immature CD34+ normal counterparts (ANOVA P<0.1%). 2 c: Phase genes corrected for normal CD34+ gene expression (ANOVA P<1×10⁻⁸). The gene expression of normal CD34+ cells was subtracted from each disease sample. The resulting pattern reflects genes associated with progression independent of normal blast biology.

FIG. 3. Genes expression signature of genes associated with specific promoter sequences. Genes with specific promoter sequences were tested for their differential enrichment across different phases of CML (see Methods). FIG. 3 a shows genes bearing a MZF promoter; FIG. 3 b shows expression of genes under putative control of delta EF1.

FIG. 4. Gene expression in Imatinib failure cases. 4 a: All CML cases including cases of imatinib failure; gene expression is based on the previously obtained ˜3,000 phase reporter set. 4 b: Cases are ranked and sorted by the correlation of summed gene expression, with cases representing the most “cp-like” and most “bc-like” forming the boundaries of gene expression patterns. Cases of imatinib failures are shown. 4 c: Genes differentially expressed in imatinib resistant cases that are not associated with progression gene set. The boxed areas represent genes differentially expressed in the imatinib resistant cases compared to blast crisis cases.

FIG. 5. Comparison of gene expression in accelerated phase versus blast phase CML. The graph shows the scatter plot of log(ratio) of all 25K genes in blast crisis and accelerated phase cases. Each blue dot represents a gene. Thus, genes in the upper left hand box are up in accelerated phase, but down in blast crisis. Genes in the upper right box are up both in accelerated and blast crisis. The gene expression levels are very highly correlated between accelerated and blast crisis (r=0.81).

FIG. 6. Phase reporter genes after removal of normal CD34+ signature. The gene expression signature of normal CD34+ cells was subtracted from the data of CML cases. The genes shown are the genes differentially expressed across disease phases after genome wide removal of CD34+ signatures (p-value of <10⁻⁴).

FIG. 7. Comparison of gene expression between bone marrow and peripheral blood. In three cases of blast crisis samples were simultaneously drawn from marrow and blood. The figures show a high correlation of gene expression for these three cases.

FIG. 8 illustrates an exemplary embodiment of a computer system for implementing the methods of this invention.

5. DETAILED DESCRIPTION OF THE INVENTION

The invention provides molecular markers, i.e., genes, the expression levels of which can be used for evaluating the progression of chronic myeloid leukemia (CML) from chronic phase to advanced phase. The identities of these markers and the measurements of their respective gene products, e.g., measurements of levels (abundances) of their encoded mRNAs or proteins, can be used by application of a pattern recognition algorithm to develop a progression classifier that discriminates between different phases of CML based on measurements of such gene products in a sample from a patient. As used herein, the term “gene product” includes mRNA transcribed from the gene and protein encoded by the gene.

Chronic myelogenous leukemia (CML) is characterized by high peripheral white blood cell (WBC) counts with granulocyte predominance and extramedullary hematopoiesis. CML typically evolves through 3 clinically distinct stages or phases: chronic phase (CP-CML or CP), accelerated phase (AP-CML or AP), and blast phase (BP-CML or BP), which is also called acute phase or blast crisis (BC-CML or BC). The chronic phase lasts several years and is characterized by accumulation of myeloid precursors and mature cells in bone marrow, peripheral blood, and extramedullary sites. During the chronic phase, patients typically have fewer than 10% blasts (or 20% blasts and promyelocytes combined) in blood or bone marrow samples. These patients usually have relatively mild symptoms and usually respond to standard treatments. The chronic phase progresses into the accelerated phase, which lasts about 4 to 6 months. During the accelerated phase, patients typically have more than 10% blasts (or 20% blasts and promyelocytes combined) but less than 30% blasts and promyelocytes in their bone marrow or blood samples. These patients often have fever, poor appetite, and weight loss. Symptoms and blood counts of an AP-CML patient are not as responsive to treatments as they are during the chronic phase. The leukemia cells often have developed new chromosomal changes, in addition to the Philadelphia chromosome. The accelerated phase progresses to the blast phase, which lasts for a few months. During the blast phase, patients typically have more than 30% blasts and promyelocytes in their bone marrow and/or blood samples. The blast cells often spread to tissues and organs beyond the bone marrow. The accelerated phase and the blast phase are often grouped together into an advanced phase of CML (ADV-CML or ADV). The molecular markers of the invention are particular useful for evaluating the progression of a CML patient from the chronic phase to the advanced phase.

The invention provides a list of genes that are differentially expressed across different phases of CML (Tables 1a and 1b, infra). This set of genes is called the phase reporter geneset. Measurements of gene products of these molecular markers, as well as of their functional equivalents, can be used for staging a CML patient. A functional equivalent with respect to a gene, designated as gene A, refers to a gene that encodes a protein or mRNA that at least partially overlaps in physiological function in the cell to that of the protein or mRNA encoded by gene A. In particular, CML staging in a patient is carried out by a method comprising determining whether the patient is in a chronic phase or an advanced phase (accelerated phase or blast phase) based on a profile of measurements (e.g., of the levels) of gene products of (i.e., encoded by) at least 5, 10, 20, 30, 40, 50, 60, 70, 80, 100, 200, 500 or all of the genes in Tables 1a and/or 1b; or of at least 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes in Tables 1a and/or 1b, or functional equivalents of such genes, in an appropriate cell sample from the patient, e.g., a bone marrow or blood sample obtained from the patient, wherein at least 1, 2, 3, 5, or 10 genes as appropriate are from Table 1a. Such a profile of measurements is also referred to herein as an “expression profile” or a “marker profile.” In a specific embodiment, the evaluation of CML progression in a patient is carried out using measurements (e.g., of the levels) of gene products of (i.e., encoded by) at least 5, 10, 20, 30, 40, 50, 60, 70, 80, 100, 200, 500 or all of the genes in Tables 1a; or of at least 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes in Tables 1a, or functional equivalents of such genes. In another specific embodiment, the evaluation of CML progression in a patient is carried out using measurements of gene products of less than 30, 40, 50, 70, 100, 200, 300, 400, or 500 total genes, in which all or at least 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes are from Tables 1a and/or 1b or their functional equivalents, or at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 of the genes are from Tables 1a and/or 1b or their functional equivalents. In one embodiment, if the patient expression profile is classified as a CP-CML profile, the patient is determined as in chronic phase, whereas if the patient expression profile is classified as a ADV-CML profile, the patient is determined as in an advanced phase (accelerated phase or blast crisis).

The invention also provides a list of genes that are associated with CML progression (Tables 2a and 2b, infra). These genes are also termed “progression genes” in the application. This set of genes is called the progression geneset. Measurements of gene products of these molecular markers, as well as of their functional equivalents, can be used for staging a CML patient. Since these genes are associated with CML progression, they are also targets for therapeutic intervention of CML. For example, a CML patient exhibiting aberrant regulation of such genes can be treated by therapies targeting such genes. Thus, measurements of gene products of these molecular markers, as well as of their functional equivalents, can also be used for determining an appropriated treatment regimen for a CML patient.

Different subcombination of CML progression genes can also be used. Thus, in various embodiments, the markers that are the genes listed in Tables 2a-2b or 3 are used. Measurements of gene products of these molecular markers and/or their functional equivalents can be used for evaluating the progression of CML in a patient. The evaluation of CML progression in a patient is carried out by a method comprising determining whether the patient is in a chronic phase or an advanced phase (accelerated phase or blast phase) based on a profile of measurements (e.g., of the levels) of gene products of (i.e., encoded by) at least 5, 10, 20, 30, 40, 50, 60, 70, 80, 100, 200 or all of the genes in Tables 2a and/or 2b, or at least 5, 10, 15 or all of the genes in Table 3; or of at least 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes in Tables 2a and/or 2b or in Table 3, or functional equivalents of such genes, in an appropriate cell sample from the patient, e.g., a bone marrow or peripheral blood sample obtained from the patient, wherein at least 1, 2, 3, 5, or 10 genes as appropriate are from Table 2a. In a specific embodiment, the evaluation of CML progression in a patient is carried out using measurements (e.g., of the levels) of gene products of (i.e., encoded by) at least 5, 10, 20, 30, 40, 50, 60, 70, 80, 100, 200, 300 or all of the genes in Tables 2a; or of at least 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes in Tables 2a, or functional equivalents of such genes. In one embodiment, if the patient expression profile is classified as a CP-CML profile, the patient is determined as in chronic phase, whereas if the patient expression profile is classified as a ADV-CML profile, the patient is determined as in an advanced phase (accelerated phase or blast crisis).

The invention also provides a list of genes that are associated with resistance to imatinib mesylate (Table 4, infra). These genes are also termed “imatinib resistance genes” in the application. This set of genes is called the imatinib resistance geneset. Measurements of gene products of these molecular markers, as well as of their functional equivalents, can be used for evaluating the responsiveness of a CML patient to imatinib treatment. The evaluation of responsiveness of a patient to imatinib is carried out by a method comprising determining whether the patient is likely to be responsive to imatinib treatment based on a profile of measurements (e.g., of the levels) of gene products of (i.e., encoded by) at least 5, 10, 20, 30, 40, 50, 60, 70, 80, 100, 200 or all of the genes in Table 4; or of at least 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the genes in Table 4, or functional equivalents of such genes, in an appropriate cell sample from the patient, e.g., a bone marrow or peripheral blood sample obtained from the patient. In one embodiment, if the patient expression profile is classified as a IM-resistance profile, the patient is determined as likely to be resistant to imatinib treatment, whereas if the patient expression profile is classified as a IM-sensitive profile, the patient is determined as likely to be responsive to imatinib treatment. In a specific embodiment, a CML patient in the chronic phase is evaluated for responsiveness to imatinib treatment based on an expression profile of such imatinib resistance genes. If the patient's expression profile indicates that the patient is likely to be resistant to imatinib treatment, bone marrow transplantation and/or other investigative treatment regimens may be assigned to the patient.

In another embodiment, the responsiveness of a CML patient to imatinib treatment can also be evaluated based on expression of phase reporters or progression genes. In this embodiment, the patient expression profile comprising measurements of phase reporter genes (Table 1a and/or 1b) or progression genes (Table 2a and/or 2b) is evaluated using a method described above. If the patient expression profile is classified as a ADV-CML profile, the patient is determined as likely to be resistant to imatinib treatment.

The measurements in the profiles of the gene products that are used can be any suitable measured values representative of the expression levels of the respective genes. The measurement of the expression level of a gene can be direct or indirect, e.g., directly of abundance levels of RNAs or proteins or indirectly, by measuring abundance levels of cDNAs, amplified RNAs or DNAs, proteins, or activity levels of RNAs or proteins, or other molecules (e.g., a metabolite) that are indicative of the foregoing. In one embodiment, the profile comprises measurements of abundances of the transcripts of the marker genes. The measurement of abundance can be a measurement of the absolute abundance of a gene product. The measurement of abundance can also be a value representative of the absolute abundance, e.g., a normalized abundance value (e.g., an abundance normalized against the abundance of a reference gene product) or an averaged abundance value (e.g., average of abundances obtained at different time points or from different tumor cell samples from the patients, or average of abundances obtained using different probes, etc.), or a combination of both. As an example, the measurement of abundance of a gene transcript can be a value obtained using an Affymetrix® GeneChip® to measure hybridization to the transcript.

In another embodiment, the expression profile is a differential expression profile comprising differential measurements of a plurality of transcripts in a sample derived from the patient versus measurements of the plurality of transcripts in a reference sample, e.g., a cell sample of normal cells. Each differential measurement in the profile can be but is not limited to an arithmetic difference, a ratio, or a log(ratio). As an example, the measurement of abundance of a gene transcript can be a value for the transcript obtained using an ink-jet array or a cDNA array in a two-color measurement. In a preferred embodiment, the reference sample comprise target polynucleotide molecules from normal cell samples (i.e., cell sample, e.g., bone marrow or peripheral blood, from those not afflicted with CML). In another preferred embodiment, the reference sample comprise target polynucleotide molecules from cell samples, e.g., bone marrow or peripheral blood, from chronic phase CML patients.

The invention also provides methods and computer systems for evaluating the progression of CML in a patient based on a measured marker profile comprising measurements of the markers of the present invention, e.g., an expression profile comprising measurements of transcripts of at least some of the genes listed in Tables 1a and/or 1b, e.g., at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 in Tables 1a and/or 1b or functional equivalents of such genes, wherein at least 1, 2, 3, 5 or 10 genes are from Table 1a. The methods and systems of the invention use a progression classifier for evaluating the progression of CML. The progression classifier can be based on any appropriate pattern recognition method (such as those described in Section 5.2) that receives an input comprising a marker profile and provides an output comprising data indicating which phase the patient belongs, i.e., chronic phase or advanced phase. The progression classifier can be constructed with training data from a plurality of CML patients for whom marker profiles and progression status are known. The plurality of patients used for training the progression classifier is also referred to herein as the training population. The training data comprise for each patient in the training population (a) a marker profile comprising measurements of gene products of a plurality of genes, respectively, in an appropriate cell sample, e.g., a bone marrow or peripheral blood sample, taken from the patient; and (b) progression status information (e.g., the CML phase of the patient). Various progression classifiers that can be used in conjunction with the present invention are described in Section 5.2., infra. In some embodiments, additional patients having known marker profiles and progression status can be used to test the accuracy of the progression classifier obtained using the training population. Such additional patients are also called “the testing population.”

The markers in the marker sets are selected based on their ability to discriminate patients having different CML phases in a plurality of CML patients for whom the progression status are known. Various methods can be used to evaluate the correlation between marker levels and CML progression. For example, genes whose expression levels are significantly different across patients in different CML phases can be identified using an appropriate statistical method, e.g., ANOVA.

The invention also provides methods and compositions for treating a patient having CML by modulating, e.g., enhancing or reducing, the expression and/or activities of one or more CML progression genes and/or target genes and/or their gene products. The invention also provides methods and compositions for treating a patient having CML by modulating, e.g., enhancing or reducing, certain CML pathways that involve in CML progression and response. The CML progression genes include those genes listed in Tables 2a and 2b. The CML target genes include those genes listed in Tables 5a and 5b. The CML pathways include FLT3; Rras2; beta-catenin; and SOCS2. The invention also provides methods and compositions for treating a patient having CML by modulating, e.g., enhancing or reducing, certain proteosomes and chaperone proteins. The invention also provides methods and compositions for treating a patient having CML by modulating genes controlled by a promoter selected from the group consisting of the following MZF, delta EF1, SPI-B, Yin Yang, and Ahr-ARNT. The invention also provides methods and compositions for treating a patient having CML by modulating, e.g., reducing, the expression and/or activity of CD47. The invention also provides methods and compositions for treating a patient having CML by targeting PRAME. The invention is based, at least in part, on the identification of aberrant regulation of these genes and pathways in CML.

Thus, the invention provides methods and compositions for treating CML by modulating the expression and/or activity of CML progression genes and/or CML target genes and/or their gene products, and/or by modulating interactions of the CML progression genes and/or target genes and/or their gene products with other proteins or molecules, e.g., substrates. The methods and compositions can be used for treating CML patient who exhibit aberrant regulation in such CML progression/target genes. Thus, such methods and compositions can be used in conjunction with imatinib mesylate. In one embodiment, the expression of one or more of the CML progression/target genes is modulated, e.g., reduced or enhanced, to treat a CML patient exhibiting aberrant regulation of these CML progression/target genes. Such modulation can be achieved by, e.g., using siRNA, antisense nucleic acid, ribozyme, and/or triple helix forming nucleic acid that target the CML progression/target genes. In another embodiment, the activity of one or more CML progression/target proteins is modulated, e.g., reduced or enhanced, to enhance the effects of chemotherapy agents. Such modulation can be achieved by, e.g., using antibodies, peptide molecules, and/or small molecules that target a CML progression/target protein.

The invention also provides methods and compositions for treating CML by modulating the expression and/or activity of imatinib mesylate resistance genes and/or their gene products, and/or by modulating interactions of the IM-resistance genes and/or their gene products with other proteins or molecules, e.g., substrates, in combination of imatinib mesylate. In one embodiment, the expression of one or more of the IM-resistance genes is modulated, e.g., reduced or enhanced, to treat a CML patient undergoing imatinib mesylate treatment. Such modulation can be achieved by, e.g., using siRNA, antisense nucleic acid, ribozyme, and/or triple helix forming nucleic acid that target the imatinib mesylate genes. In another embodiment, the activity of one or more imatinib mesylate proteins is modulated, e.g., reduced or enhanced, to enhance the effects of chemotherapy agents. Such modulation can be achieved by, e.g., using antibodies, peptide molecules, and/or small molecules that target imatinib mesylate proteins.

The invention also provides methods and compositions for utilizing CML progression/target genes or IM-resistance genes, and/or their products for screening for agents that modulate their expression and/or activity and/or modulating their interactions with other proteins or molecules. Agents that modulate expression and/or activity of CML progression/target genes can be used for treating CML patient exhibiting aberrant regulation of one or more CML progression/target genes. Agents that modulate expression and/or activity of IM-resistance genes can be used in combination with IM for treating CML patient exhibiting resistance to IM treatment. Thus, the invention provides methods and compositions for utilizing CML progression/target genes and gene products for screening for agents that are useful in modulating expression and/or activity of CML progression/target genes or IM resistance genes and/or their products and/or modulating their interactions with other proteins or molecules in a CML patient exhibiting aberrant regulation of one or more CML progression/target genes or IM resistance genes. The compositions of the invention include but not limited to siRNA, antisense nucleic acid, ribozyme, triple helix forming nucleic acid, antibody, peptide or polypeptide molecules, and small organic or inorganic molecules.

The present invention also provides methods and compositions for identifying other extra- or intra-cellular molecules, e.g., genes and proteins, which interacts with the CML progression/target genes or IM resistance genes, and/or their gene products, and/or CML progression pathways. The present invention also provides methods and compositions for treating CML by modulating such cellular constituents and/or pathways.

As used herein, a patient is an animal having CML. The patient can be but is not limited to a human, or, in a veterinary context, from non-human animals such as ruminants, horses, swine or sheep, or from domestic companion animals such as felines and canines. In a preferred embodiment, the patient is a human patient. Suitable samples that can be used in conjunction with the present invention include but are not limited to bone marrow samples and peripheral blood samples.

5.1. Genes Associated with CML Progression and Response

The invention provides molecular marker sets (of genes) that can be used for evaluating progression and/or imatinib resistance in a CML patient based on a profile of the markers in the marker set (containing measurements of marker gene products).

Tables 1a and 1b list genes that are differentially expressed across different phases of CML. This set of genes is called the phase reporter geneset. The phase reporter genes are identified by their SEQ ID NOs in Tables 1a and 1b. Tables 1a and 1b also listed for each gene the log ratio of expression level of the gene in samples from patients of a particular phase (e.g., CP, AP, or BC) versus expression level of the gene in a pool of CML bone marrow samples from chronic phase patients. Each log ratio column thus contains expression levels of markers for a particular phase. Information for these genes is presented in Table 8. In Table 8, the following information is presented for each gene: gene identifier (column 1), gene name (column 2), the SEQ ID NO of the sequence of the gene (column 3), and the SEQ ID NO of the probe sequence used in the present application (column 4). The first column of Table 8 shows the identifiers of genes disclosed in the application. The term “SUBS” is shorthand for substance identifier. For those genes listed in Table 8 that have a GenBank® accession number, the GenBank® accession number is listed. For those genes in Table 8 that do not have a GenBank® Accession No, the Contig ID numbers of the transcript sequences in the Phil Green assembly (Nat Genet 2000 June; 25(2):232-4) is listed. Phil Green's group at the University of Washington assembled ESTs from the Washington University-Merck Human EST Project and CGAP archives. Analysis of expressed sequence tags indicates 35,000 human genes (Nat Genet 2000 June; 25(2):232-4). This assembly, dated Mar. 17, 2000, resulted in 62,064 contigs representing 795,000 ESTs. These contigs have the word “contig” included in their identifiers. Table 1a lists phase reporters that were not disclosed in U.S. Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003. Table 1b lists phase reporters that were also identified in U.S. Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003.

TABLE 1a phase reporter genes SEQ ID log(ratio) NO CP log(ratio) AP log(ratio) BC 1 −0.00406 0.196563 0.331631 2 −0.013036 0.331191 0.13619 3 −0.01517 −0.1969 −0.51997 4 −0.01226 0.234703 0.506317 5 −0.01055 −0.11513 −0.25239 6 0.02333 0.2234 0.385294 7 0.001109 −0.04225 −0.38922 8 0.022178 0.320491 0.362686 9 −0.01332 −0.22505 −0.26552 10 0.002491 0.107514 0.40248 11 −0.03342 −0.12983 −0.34856 12 −0.02396 −0.1739 −0.56037 13 0.004316 −0.16534 −0.15954 14 −0.00225 0.464357 0.637155 15 −0.06413 −0.10146 −0.58794 16 0.009128 0.235874 0.469511 17 0.020236 1.123603 0.742981 18 0.016214 0.159637 0.392829 19 −0.04723 −0.47509 −1.36264 21 −0.01095 0.232221 0.294685 22 0.012172 0.427707 0.729027 23 −0.01999 −0.21291 −0.36149 24 −0.00972 −0.14706 −0.4052 25 0.004981 −0.21328 −0.37135 26 −0.02611 −0.30231 −0.45226 27 0.010514 0.338824 0.434019 29 −0.02088 −0.283 −0.45987 30 −0.00198 −0.11265 −0.28724 31 0.023577 0.770737 0.690215 32 0.008671 −0.0801 −0.28421 33 0.012103 −0.15124 −0.15019 34 0.010651 −0.14341 −0.515 35 −0.00126 0.010489 0.264385 36 0.027348 0.34774 0.624742 37 0.033762 0.213053 0.520588 38 0.003765 −0.14306 −0.39624 39 0.033025 0.281292 0.406565 40 −0.06315 −0.28017 −1.14257 41 0.007748 0.09581 0.335903 42 −0.01732 −0.09377 −0.68791 43 0.018086 −0.22492 −0.285 44 0.014232 −0.27373 −0.31289 45 0.036197 0.142295 0.466937 46 −0.01022 0.299737 0.425197 47 0.006822 0.199214 0.443601 48 0.021602 0.186392 0.33675 49 −0.03649 −0.26722 −0.49009 52 0.008248 0.502971 0.507442 53 0.040187 0.687502 0.564688 54 −0.00051 −0.10576 −0.40709 55 −0.01352 −0.22612 −0.49128 57 −0.05265 0.433648 0.40219 58 0.019239 0.187127 0.325353 59 0.006451 −0.22186 −0.18506 60 0.010201 0.615117 1.017473 61 0.013254 −0.23449 −0.26153 62 0.012036 −0.20146 −0.36216 63 0.018656 0.262829 0.530868 64 −0.01623 −0.1428 −0.50841 66 −0.00346 −0.1026 −0.30257 67 0.009841 0.335299 0.527591 68 0.009665 0.97143 0.990692 69 −0.03517 0.36588 0.442864 71 0.005961 −0.17466 −0.20803 73 −0.00646 −0.25708 −0.21749 74 −0.018621 0.110352 −0.541362 75 −0.00408 −0.21342 −0.26897 76 0.009207 0.769453 0.850508 78 0.0123 0.167805 0.337085 79 0.00674 −0.17218 −0.25414 80 −0.00232 −0.13768 −0.25962 81 −0.04268 −0.09565 −0.76123 82 −0.00889 −0.18131 −0.3448 83 0.00964 0.139417 0.328274 84 −0.03477 0.147022 −0.67052 85 −0.0546 −0.22956 −1.32988 86 −0.01987 −0.41057 −0.63814 87 −0.00053 −0.16512 −0.19246 89 0.029134 0.166704 0.399066 90 −0.00832 −0.13645 −0.3186 92 0.037155 0.284153 0.64532 94 −0.01142 −0.13881 −0.3608 95 0.01125 0.10955 0.227757 96 0.012527 0.229295 0.293851 98 0.060257 0.952532 0.999368 100 −0.0643 −0.33585 −0.59098 101 0.009363 0.184372 0.293381 102 −0.0128 −0.2329 −0.54422 103 0.019799 0.472863 0.54563 104 0.039449 0.415733 0.576671 106 0.010496 −0.12076 −0.18666 107 0.011423 −0.16555 −0.23653 108 −0.08443 1.178885 0.802082 109 0.013994 0.264328 0.401994 110 0.04438 0.40653 0.580366 111 0.027108 0.265955 0.604212 112 0.003332 −0.25986 −0.29846 113 −0.01029 −0.26712 −0.2846 114 −0.05586 −0.21334 −0.82293 115 0.009594 0.017981 0.208686 117 −0.01023 0.452998 0.673941 118 −0.00659 0.490457 0.517515 119 −0.02254 0.744289 0.818592 120 −0.01441 −0.29009 −0.5309 121 −0.01153 −0.19616 −0.33788 122 0.028602 0.405315 0.525104 123 −0.00564 0.355702 0.57473 124 0.005664 0.194653 0.230888 125 0.029794 0.454278 0.726423 126 −0.01071 −0.33686 −0.43968 127 0.037702 0.541984 0.729726 128 −0.00753 0.139932 0.246875 129 0.024429 1.375049 1.029358 130 −0.01338 −0.13678 −0.28729 131 0.014108 0.432232 0.771513 132 0.026976 0.425544 0.61667 133 0.024633 0.146129 0.39073 135 −0.00713 −0.09868 −0.64744 136 −0.03239 −0.08145 −0.37526 137 −0.04003 −0.24301 −0.62499 138 −0.00308 0.502829 0.723824 139 0.006495 0.731382 0.863995 140 0.001806 −0.20936 −0.37679 141 −0.03144 −0.20901 −0.55634 143 0.007968 −0.15803 −0.23468 144 −0.03705 −0.14512 −0.62385 145 0.027758 0.144793 0.533543 146 −0.01241 −0.08289 −0.71342 147 0.024977 −0.11774 −0.37273 148 −0.03021 −0.24989 −0.41756 149 −0.07893 −0.2035 −1.0393 151 0.000992 0.489396 0.562018 152 −0.03269 −0.19994 −0.50103 153 −0.01351 −0.07093 −0.35161 154 0.020101 0.132417 0.359255 156 −0.02182 −0.18751 −0.49204 157 0.00543 −0.2313 −0.38327 159 −0.02675 −0.26775 −0.37637 160 −0.10326 −0.41976 −1.24875 161 −0.06485 −0.23089 −1.08897 162 0.010219 −0.24712 −0.31122 163 0.00622 0.175804 0.334146 164 0.008023 0.275526 0.371384 165 −0.0136 −0.18292 −0.50396 166 −0.04425 −0.16366 −0.88014 167 0.012461 0.406484 0.521279 168 −0.00562 −0.17893 −0.63614 169 −0.0054 0.165872 0.354167 170 −0.02256 −0.17498 −0.38989 172 0.011677 0.261214 0.340198 173 0.020232 0.307823 0.428941 175 0.013073 0.300556 0.463354 176 0.003276 0.347293 0.31246 178 0.009824 0.232776 0.381628 179 −0.02289 −0.25739 −0.3302 180 0.009575 0.390154 0.620031 181 0.006626 0.466249 0.426852 182 0.006874 −0.17448 −0.30214 183 −0.04255 −0.18274 −0.56752 185 0.022986 0.276936 0.409773 186 0.035638 0.396599 0.57451 187 −0.03048 0.29151 0.498925 188 0.018337 0.150771 0.433259 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3507 0.018668 0.097833 0.194468 3508 0.016448 0.115095 0.227688 3509 0.013763 0.120072 0.2309 3510 −0.00176 0.172136 0.392661 3511 0.033154 0.422828 0.502533 3512 0.019004 0.260874 0.605656 3513 0.00474 0.123786 0.272245 3515 0.003764 0.25854 0.35417 3516 0.006238 −0.19753 −0.1929 3517 0.00654 0.031032 0.211139 3518 0.007711 0.025393 0.337297 3519 0.021036 0.127258 0.316529 3520 −0.01732 −0.17969 −1.05816 3521 −0.03832 −0.14892 −0.64816 3522 0.002699 0.336047 0.755432 3523 0.0272 0.063065 0.326339 3524 0.007645 −0.13807 −0.11901 3525 −0.0046 0.114568 0.217153 3526 −0.00152 −0.26116 −0.28321 3527 −0.02135 −0.26583 −0.57971 3528 0.025288 0.347945 0.459399 3529 −0.06764 −0.29288 −0.81872 3530 0.021277 0.154993 0.324106 3531 −0.000032 0.213466 0.316182 3532 −0.02307 0.383006 0.430598 3534 0.006069 0.248446 0.367867 3535 −0.01309 −0.25375 −0.68693 3536 0.014569 0.235339 0.390802 3537 0.008394 0.36569 0.441899 3539 0.029654 0.190536 0.223447 3540 0.022659 0.287814 0.460905 3541 −0.0021 0.170309 0.289484 3542 −0.01138 −0.18146 −0.32578 3543 −0.01974 −0.2489 −0.27214 3544 0.027074 0.424713 0.675614 3545 −0.07683 −0.51183 −1.36912 3547 0.000021 0.094057 0.223268 3548 0.011955 0.28919 0.485465 3549 0.023904 0.428122 0.680776 3550 −0.03893 −0.19043 −0.68542 3551 −0.07238 −0.3147 −1.46004 3552 0.015569 0.282794 0.347364 3553 −0.00688 0.272823 0.325358 3556 0.04665 0.338627 0.457554 3557 0.014913 0.201938 0.4141 3558 0.032499 0.074678 0.253153 3559 0.008088 0.301892 0.453923 3560 0.004516 0.219196 0.385653 3561 −0.00872 −0.14402 −0.3015 3562 0.011229 0.19481 0.270765 3563 0.002252 0.197059 0.467898 3564 0.004196 −0.17839 −0.35812 3565 0.005919 0.433496 0.704711 3566 0.014141 0.259842 0.625664 3567 0.002687 −0.07275 −0.16865 3568 0.019386 0.180756 0.320826 3569 0.008055 0.236448 0.463364 3570 −0.00885 −0.19005 −0.18943 3571 −0.01066 −0.2524 −0.31281 3572 0.003586 0.175294 0.33668 3573 0.003077 −0.16699 −0.2679 3574 0.010204 −0.24174 −0.21023 3575 −0.01722 −0.23788 −0.5273 3576 −0.00986 −0.15833 −0.35006 3577 0.002417 0.115933 0.275389 3578 0.01931 0.128265 0.257442 3579 −0.00892 −0.21633 −0.26341 3580 −0.00471 −0.23215 −0.4848 3581 0.020012 −0.19936 −0.17456 3582 −0.03815 −0.31028 −0.83405 3583 0.050287 −0.01954 0.220994 3584 −0.00585 −0.12787 −0.3086 3585 −0.00877 0.285035 0.313925 3586 0.023951 0.461968 0.522236 3587 −0.03648 −0.06649 −0.96644 3588 −0.0798 −0.35864 −0.6144.4 3589 −0.01895 −0.18531 −0.59784 3590 −0.00434 −0.0927 −0.57452 3591 −0.01872 −0.15803 −0.39983 3592 0.034991 0.443566 0.697839 3593 0.003399 −0.19622 −0.33779 3594 −0.00647 −0.26511 −0.28231 3595 0.02467 0.206796 0.445373 3596 −0.05031 −0.1575 −0.48587 3597 0.01621 −0.09026 −0.15802 3598 0.012908 −0.04883 −0.1707 3599 −0.00487 −0.18513 −0.31987 3600 −0.00359 −0.15119 −0.29052 3601 −0.0151 −0.13785 −0.44486 3602 −0.0169 −0.22645 −0.42297 3603 0.005186 −0.17402 −0.16865 3604 −0.05188 0.315535 0.632687 3605 0.023942 0.83018 0.88166 3606 0.025262 0.245762 0.342364 3607 0.011981 −0.24067 −0.45907 3608 0.00673 0.18853 0.415095 3609 −0.01799 −0.22257 −0.34049 3610 −0.01097 −0.04613 −0.41743 3612 −0.01484 −0.1804 −0.4596 3613 0.000939 0.263793 0.678549 3614 0.006779 −0.2545 −0.29857 3615 0.015733 0.199486 0.348857 3616 0.027123 0.254658 0.40739 3617 −0.02985 −0.1815 −0.3909 3618 −0.05222 −0.31387 −0.6686 3619 0.012011 0.093853 0.436918 3621 −0.03416 −0.08213 −0.7659 3622 0.012578 −0.13075 −0.23829 3623 −0.000007 0.238639 0.514736 3624 −0.01407 −0.01854 −0.6361 3625 0.03931 0.356907 0.463023 3626 0.018908 0.155317 0.368218 3627 −0.018961 −0.122255 −0.455286 3628 0.014716 0.206784 0.434224 3629 −0.07553 −0.33141 −0.9787 3630 0.015157 0.273984 0.247117 3631 −0.00033 0.200936 0.41693 3633 0.007665 0.242867 0.368278 3634 0.009517 0.749121 0.730716 3635 −0.00042 −0.03395 −0.27982 3636 0.014869 0.177299 0.385549 3637 −0.00089 0.343397 0.523406 3638 −0.01318 −0.24177 −0.26026 3639 0.015299 0.166454 0.312326 3641 −0.02405 −0.22617 −0.36482 3643 −0.01067 −0.22275 −0.30837 3644 0.015624 0.272495 0.42811 3645 0.02679 0.139602 0.304642 3647 0.016106 −0.23904 −0.34971 3648 −0.00785 0.415134 0.576215 3649 −0.03814 −0.24153 −0.62728 3651 −0.00168 0.178946 0.296663 3652 0.005417 0.201231 0.293373 3653 0.020992 0.098499 0.323563 3654 0.009897 0.171846 0.304385 3655 −0.009543 −0.030372 0.280245 3656 0.005039 0.109044 0.437077 3657 0.009618 −0.13852 −0.34652 3658 0.010488 −0.100563 −0.316822 3659 0.022109 0.00349 0.254205 3660 −0.02924 0.248024 0.349343 3661 −0.01618 −0.25316 −0.5936 3662 −0.00179 −0.29298 −0.4016 3663 0.010692 0.195257 0.259274 3664 −0.02055 −0.16417 −0.63881 3665 0.006512 −0.20855 −0.22497 3666 0.014762 0.130635 0.27316 3667 0.005038 −0.15002 −0.3011 3668 −0.0037 0.161125 0.440317 3669 −0.01488 0.17173 0.377036 3670 0.004662 0.204447 0.405003 3671 0.031363 0.225054 0.391684 3672 −0.01716 0.363938 0.454998 3673 −0.02599 −0.26151 −0.85852 3674 0.007781 0.240323 0.617296 3675 0.017188 0.381003 0.584545 3676 −0.01941 −0.18262 −0.52435 3678 −0.07755 −0.25462 −1.21457 3679 0.029503 0.26528 0.545758 3680 −0.01146 −0.05606 −0.57839 3681 0.02916 0.284717 0.399181 3682 0.031311 0.886442 1.043437 3684 −0.05039 −0.22784 −0.67536 3687 0.025134 0.077778 0.233685 3688 −0.03452 −0.2365 −0.6591 3689 0.020959 0.135435 0.442065 3690 −0.00061 −0.22418 −0.21696 3691 0.030615 0.368867 0.463789 3693 0.008242 0.13538 0.238988 3694 0.022164 0.24485 0.369787 3695 0.008348 0.345415 0.445491 3697 0.027044 0.275282 0.423066 3698 0.008222 0.350065 0.740909 3699 −0.00952 −0.19156 −0.22617 3700 −0.00774 −0.16099 −0.19923 3701 −0.05313 −0.33669 −0.5235 3702 0.003856 0.209935 0.358961 3703 0.007194 −0.37491 −0.31409 3704 0.001122 0.2761 0.371209 3705 −0.00709 0.357332 0.489837 3706 0.040931 0.462946 0.60049 3707 −0.00516 0.271088 0.294429 3708 0.00797 0.305948 0.372261 3709 −0.01333 −0.34526 −0.32565 3710 −0.00842 0.743893 0.603555 3712 0.005041 −0.17492 −0.29702 3713 −0.0289 −0.19531 −0.40228 3714 0.011165 0.155011 0.279136 3715 −0.00133 0.390666 0.773649 3716 0.021292 0.217723 0.532074 3717 0.029764 0.133139 0.363509 3719 −0.00569 0.272222 0.395599 3720 0.006975 0.316981 −0.554667 3721 −0.00718 0.174198 0.213069 3722 −0.01824 −0.14028 −0.55819 3723 0.001449 0.433877 0.750806 3724 −0.06438 −0.34026 −0.90631 3726 0.016783 0.074532 0.32937 3727 −0.023638 −0.142935 −0.651747 3728 0.005353 0.185561 0.374248 3729 0.015333 0.466716 0.338765 3730 −0.11273 −0.34033 −0.74304 3731 −0.052 −0.44987 −1.00602 3732 0.001521 0.087123 0.219262 3733 −0.00774 0.297037 0.411744 3734 0.007834 −0.27308 −0.2795 3735 −0.0003 0.1427 0.284445 3736 −0.00304 0.247981 0.419058 3737 −0.05269 −0.14303 −0.9691 3738 0.058799 0.23747 0.50269 3739 −0.02901 −0.34538 −0.60565 3740 0.008498 0.100432 0.280781 3741 −0.0008 0.258263 0.455968 3742 −0.04584 0.066503 0.375283 3743 −0.03349 0.288905 0.502598 3744 −0.04514 −0.31129 −1.31612 3745 0.008607 0.236502 0.379077 3747 0.025051 0.654614 0.673397 3748 −0.00402 −0.23433 −0.60235 3749 −0.03559 1.065448 1.023898 3750 −0.02419 0.213775 0.639856 3751 −0.03336 −0.27007 −0.76418 3752 −0.0443 0.339835 0.498822 3753 −0.01658 0.10543 0.226121 3754 0.009493 0.275559 0.623179 3755 −0.021919 0.195442 0.379175 3756 0.007138 0.218329 0.357365 3757 −0.00525 −0.21511 −0.32728 3758 0.012473 0.201175 0.362596 3759 −0.01279 −0.2507 −0.53842 3760 0.025025 0.151079 0.286126 3761 0.013849 0.149988 0.305557 3762 −0.02366 −0.28636 −0.81937 3764 −0.01564 −0.19303 −0.26092 3766 −0.0078 0.33788 0.559023 3767 −0.14766 −0.58681 −0.8303 3768 −0.02365 −0.02657 −0.40423 3769 −0.07505 −0.45329 −0.81364 3770 0.014256 0.252952 0.791686 3771 0.000762 0.414331 0.473745 3772 −0.04075 −0.10969 −0.87339 3773 0.009132 −0.19384 −0.26354 3774 0.006782 0.308886 0.586722 3775 0.016697 −0.13758 −0.22465 3776 −0.00641 −0.09848 −0.32179 3777 −0.01008 −0.30175 −0.74848 3778 −0.18892 −0.16936 −0.96093 3779 0.015198 0.460693 0.920111 3780 −0.00343 0.30979 0.443498 3781 0.007713 −0.22269 −0.19107 3782 −0.00516 −0.21752 −0.43031 3783 0.008031 −0.275 −0.26959 3784 0.001544 0.152755 0.22911 3786 0.033983 0.314454 0.467167 3787 −0.00797 −0.17558 −0.34756 3788 −0.01013 0.252803 0.451763 3789 0.011368 −0.17659 −0.27607 3790 −0.01187 0.559225 0.865392 3791 0.007796 −0.11536 −0.75804 3794 −0.02133 −0.24973 −0.60104 3795 0.006022 −0.33209 −0.26862 3796 0.010623 0.370266 0.38694 3797 0.014382 −0.13074 −0.1862 3798 −0.00565 −0.31968 −0.72164 3799 −0.00825 −0.25969 −0.45754 3801 −0.00696 −0.08637 −0.25043 3802 0.017105 0.245965 0.524084 3803 0.012106 −0.10429 −0.39847 3805 0.000356 0.413256 0.478106 3806 0.010934 0.29635 0.386202 3807 0.000112 −0.09254 −0.20172 3808 −0.029 −0.27661 −0.49614 3809 0.010957 0.143925 0.427276 3810 0.013606 0.288317 0.384979 3811 0.00107 −0.14349 −0.23862 3813 0.015757 0.049963 0.322916 3814 0.012775 0.268704 0.489882 3815 −0.00178 −0.24858 −0.55539 3816 0.020478 0.328518 0.363496 3817 0.024418 0.191881 0.339502 3818 −0.01942 −0.29161 −0.28157 3819 0.000103 0.270294 0.325421 3820 −0.01143 0.488676 1.0676 3821 −0.00952 0.403054 0.422651 3822 0.009236 −0.18298 −0.28602 3823 −0.00386 −0.02828 −0.23222 3824 0.014109 0.222256 0.352421 3825 0.02032 0.265215 0.459123 3826 0.033585 0.252623 0.438713 3827 −0.03236 −0.26125 −0.51846 3828 0.034594 0.156209 0.285878 3829 0.020227 0.248677 0.346795 3830 0.014978 0.091181 0.209185 3831 −0.00336 −0.26565 −0.32013 3832 −0.01958 −0.3121 −0.42927 3833 0.026113 0.382008 0.532301 3834 0.023708 −0.1401 −0.30331 3835 0.005344 0.232229 0.33731 3837 0.015978 0.148698 0.33504 3838 −0.06039 −0.39414 −1.08079 3839 −0.05249 −0.43012 −0.97039 3840 0.035352 0.420428 0.634365 3841 0.014726 0.065969 0.296027 3842 0.014931 0.337795 0.48071 3843 0.000632 0.084208 0.363903 3846 −0.12428 −0.61888 −1.14868 3847 0.024094 0.242898 0.532951 3848 0.014222 −0.20545 −0.18744 3850 −0.0071 −0.39614 −1.31291 3851 0.012684 0.070752 0.274745 3852 0.02372 0.172396 0.342361 3853 0.00189 −0.145487 −0.229147 3854 −0.00101 −0.21912 −0.72961 3855 0.007222 −0.15336 −0.26965 3856 0.007543 −0.15408 −0.15187 3858 0.018762 −0.28212 −0.40115 3859 −0.08983 −0.08099 −0.96191 3860 0.004134 0.11989 0.775235 3861 −0.00476 0.799769 0.775464 3862 −0.02069 0.619347 0.552404 3863 0.023825 0.198966 0.288914 3864 0.002065 −0.18112 −0.3627 3865 0.023799 0.373823 0.502792 3866 −0.07514 −0.16355 −1.15587 3867 −0.02357 0.426881 0.768005 3868 −0.06742 −0.22372 −1.48362 3869 0.007952 −0.20656 −0.18147 3870 −0.00995 −0.18825 −0.32561 3871 −0.09391 −0.49811 −0.67155 3872 −0.01577 −0.30748 −0.36469 3873 0.00135 −0.177 −0.26574 3874 0.01437 −0.27493 −0.64992 3875 0.008601 0.175417 0.368725 3877 0.0215 0.239552 0.543968 3878 0.007867 −0.14612 −0.219 3879 −0.02127 −0.13431 −0.5214 3881 −0.01449 −0.22729 −0.38659 3882 −0.008 −0.28045 −0.35033 3883 −0.00282 −0.22456 −0.3246 3884 −0.01006 0.125335 0.437432 3885 −0.0341 −0.33793 −0.64981 3886 −0.02831 −0.22518 −0.44843 3887 −0.00342 −0.15249 −0.46289 3888 0.014393 0.484554 0.495931 3889 0.001776 0.262078 0.383028 3890 0.011023 −0.01062 −0.44164 3892 0.004332 −0.00059 −0.38242 3893 0.001464 −0.14286 −0.18126 3894 −0.01231 −0.2316 −0.32005 3895 0.018186 0.089257 0.210466 3896 0.0075 −0.17357 −0.27499 3897 −0.00568 −0.14148 −0.37829 3898 0.002511 −0.14907 −0.15297 3899 −0.0092 −0.1654 −0.41466 3900 0.01744 0.108167 0.303529 3902 −0.21525 −0.62727 −0.88264 3903 0.012294 0.101754 0.422339 3904 0.007328 −0.12993 −0.17647 3906 0.032547 0.2237 0.374842 3907 0.020824 0.455249 0.666732 3908 0.001958 −0.08941 −0.20901 3909 −0.03403 −0.28041 −0.66761 3910 0.005124 0.373303 0.456396 3911 0.007527 0.436713 0.635286 3912 −0.01004 −0.18805 −0.1945 3913 −0.13841 0.130768 −0.78612 3914 0.005593 −0.24982 −0.45921 3916 0.007871 0.294561 0.472056 3917 0.000456 0.350453 0.512085 3918 −0.00721 −0.20685 −0.30782 3919 0.00249 0.4553 0.467418 3920 0.003433 0.234106 0.347743 3921 0.02159 0.267666 0.272491 3922 −0.01034 −0.23596 −0.40316 3923 −0.0218 −0.17331 −0.31503 3924 −0.01052 −0.2608 −0.45258 3926 0.005481 −0.19415 −0.38862 3927 −0.00198 −0.15223 −0.26378 3928 −0.00481 −0.19212 −0.60011 3929 −0.02907 −0.31237 −0.67115 3930 0.018932 0.502499 0.630779 3931 0.007823 0.330178 0.374828 3932 −0.00625 −0.19177 −0.36188 3934 −0.01138 −0.16719 −0.62327 3936 0.013418 −0.12059 −0.21994 3937 −0.00602 −0.17249 −0.19886 3938 −0.00093 −0.18338 −0.21621 3940 −0.0063 0.32237 0.447277 3941 −0.03123 0.753525 1.028617 3942 −0.03893 −0.15886 −1.03693 3943 0.016177 0.318878 0.500708 3944 0.029472 −0.14649 −0.37317 3945 −0.15185 −0.49868 −0.607 3946 −0.09644 −0.46037 −0.57596 3948 0.010157 0.279247 0.48872 3949 0.002141 −0.34666 −0.2661 3950 −0.03206 −0.28804 −0.36911 3951 0.006273 0.122116 0.414685 3952 −0.04024 0.176953 0.383377 3953 0.0072 −0.23691 −0.34253 3954 0.012744 −0.16741 −0.24655 3955 −0.019735 −0.159647 −0.33003 3957 −0.00172 0.066009 0.290683 3958 0.000007 0.258618 0.366426 3959 −0.07307 −0.35372 −0.42584 3960 −0.005 −0.29445 −0.89736 3962 −0.00971 −0.14007 −0.77128 3963 −0.0012 −0.19036 −0.18134 3964 −0.00871 −0.31654 −0.73351 3965 0.007545 −0.19764 −0.31117 3967 −0.09077 −0.42429 −0.50192 3968 0.002684 −0.24249 −0.27393

TABLE 1b phase reporter genes SEQ ID NO log(ratio) CP log(ratio) AP log(ratio) BC 56 −0.01844 −0.2843 −0.52572 65 −0.043 −0.27935 −0.61442 70 −0.02677 0.321263 0.479287 177 −0.02343 −0.25951 −0.53988 190 −0.04631 −0.22027 −0.61104 199 −0.19435 −0.66091 −1.74771 1758 −0.0427 −0.06237 −0.68566 1773 0.032164 0.295407 0.487261 1774 0.02296 0.304684 0.561645 1786 0.014041 0.225619 0.584752 1815 0.035253 0.254518 0.53063 1823 0.014591 0.300107 0.456781 3925 −0.04398 −0.3128 −0.99975 3933 −0.0347 −0.12523 −0.74375 3947 −0.04231 −0.53589 −1.45253 3956 −0.00856 −0.16684 −0.95119

Tables 2a and 2b list a set of 386 progression genes identified by searching for phase reporter genes after removing CD34 content (p<10⁻⁸) (the “progression geneset”). The CD34 content is removed by subtracting the expression level of each gene in a sample of CD34+ cells from the expression level of the gene in a tumor sample from a CML patient. The progression genes are identified by their SEQ ID NOs in Tables 2a and 2b. Information for these genes is presented in Table 8. Table 2a lists progression genes that were not disclosed in U.S. Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003. Table 2b lists progression genes that were also identified in U.S. Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003. Tables 2a and 2b also listed for each gene the log ratio of CD34+(−) expression level of the gene (i.e., the expression level of the gene in a tumor sample from a CML patient minus the expression level of the gene in a sample of CD34+ cells) in samples from patients of a particular phase (e.g., CP, AP, or BC) versus CD34+(−) expression level of the gene in a pool of CML bone marrow samples from chronic phase patients. Each log ratio column thus contains expression levels of markers for a particular phase.

TABLE 2a progression genes SEQ ID NO log(ratio) CP log(ratio) AP log(ratio) BC 2 −0.013036 0.331191 0.13619 22 −0.027625 0.25124 0.297168 44 −0.008283 −0.175784 −0.35176 74 −0.018621 0.110352 −0.541362 75 0.012898 −0.15485 −0.081578 98 −0.0065 0.226199 0.384576 118 0.0235 0.413795 0.572899 120 −0.068801 −0.238346 −0.788486 123 −0.014776 0.153884 0.315337 127 0.014361 0.2732 0.196317 146 −0.062898 −0.026859 −0.467529 166 −0.008117 −0.02223 −0.588809 192 −0.03375 −0.376045 −0.824014 201 −0.046038 0.745451 0.938831 252 −0.011159 −0.181168 −0.338022 260 −0.014983 0.169381 0.378207 261 0.002136 −0.013939 0.252784 277 −0.059071 0.153895 −0.707755 282 −0.011292 0.246831 0.217263 300 −0.015553 0.264616 0.213715 312 −0.006268 −0.169392 −0.415121 321 0.017293 0.264073 0.351815 329 0.015519 −0.110525 −0.132442 348 0.003377 0.292866 0.385025 359 0.011735 −0.238758 −0.159133 361 0.0199 −0.29195 −0.308127 369 0.015105 −0.30705 −0.467622 379 0.011972 0.153175 0.287232 382 −0.034613 0.539856 0.385649 392 −0.018091 0.211741 0.151359 397 0.001911 −0.204817 −0.142157 398 −0.055256 0.454774 0.463563 401 0.010902 −0.0223 −0.435077 407 0.022957 −0.146156 −0.144178 408 0.000587 0.042633 0.171636 413 −0.004104 −0.021944 −0.541188 432 −0.021105 0.318234 0.36938 453 0.000187 −0.016503 −0.233794 462 0.015733 −0.049378 −0.203749 464 −0.007901 −0.242419 −0.192786 468 −0.069818 0.055712 −0.792861 483 0.022087 0.013675 −0.264371 487 −0.044506 −0.226859 −0.730255 490 0.032225 0.697253 0.473438 493 0.005365 0.117615 0.279824 506 0.002222 0.244418 0.413136 508 −0.001048 0.149848 0.252886 513 −0.025942 0.105185 −0.589267 532 0.013898 −0.091144 −0.105794 535 −0.02973 0.31094 −0.640132 549 −0.024057 −0.192808 −0.507538 562 −0.007465 −0.085295 −0.451408 564 0.010706 0.16159 0.377863 565 −0.013377 0.189935 0.358398 596 −0.027369 −0.300983 −0.676728 602 −0.02947 0.152602 0.288592 607 −0.03208 0.163679 0.433561 629 −0.017135 0.164754 0.393246 631 −0.005919 0.029702 0.182895 638 0.005995 0.158171 0.295784 641 −0.002351 0.141381 −0.371398 644 0.011035 −0.188829 −0.236191 648 −0.000305 0.09399 0.156447 671 −0.052686 0.224817 −0.778464 678 −0.011662 −0.03032 −0.483853 686 −0.044146 0.393448 0.352519 687 0.004128 0.014188 0.147004 688 −0.007112 0.135577 −0.384238 692 0.01078 −0.193913 −0.339249 694 0.026903 0.238728 0.198984 699 0.002836 −0.136336 −0.204499 700 −0.003573 0.186663 0.111998 702 −0.004795 0.43693 0.231795 704 0.008652 0.448527 0.623811 708 0.035423 −0.072534 −0.243577 710 0.00051 −0.260385 −0.325256 715 −0.031368 −0.034762 −0.28179 725 0.018721 −0.110491 −0.07631 727 0.011701 0.352484 0.599663 730 0.007214 −0.100867 −0.390067 739 −0.021549 0.313399 0.230556 758 0.006066 0.197232 0.154028 774 −0.011428 0.297906 0.460758 781 0.049464 0.661373 0.621414 789 −0.011135 0.073025 0.220549 794 0.00587 −0.124811 −0.092198 852 −0.009777 0.061913 0.217413 862 0.012512 0.101103 0.346959 878 −0.007159 0.624676 0.342539 879 0.015292 0.310113 −0.619546 902 0.01057 0.108517 0.282889 906 0.009153 0.106628 0.432846 912 −0.03355 −0.086456 −0.556116 913 −0.002153 −0.162393 −0.176945 934 −0.001515 0.49437 0.349162 949 −0.009006 −0.003959 −0.260665 969 0.009521 −0.194416 −0.088755 983 −0.009189 −0.179037 −0.279808 984 0.003783 0.428077 −0.304577 995 0.018194 0.115536 0.453015 1005 −0.004206 0.264613 0.406912 1006 0.013715 0.253173 −0.48171 1014 −0.027032 0.218431 0.369874 1027 −0.097802 0.14838 −0.409138 1030 0.012193 −0.156904 −0.129918 1036 0.018457 0.150121 0.282032 1042 0.016406 0.12399 0.254155 1047 −0.010956 0.160388 0.293704 1053 −0.003597 0.168234 0.188554 1065 0.041337 0.356808 0.457428 1086 0.012167 0.126556 0.308808 1089 −0.056921 0.265345 0.488138 1092 0.031164 0.741399 0.650443 1093 −0.019458 0.265262 0.281598 1100 −0.026376 −0.107488 0.120579 1105 0.000402 0.241675 0.374547 1106 0.013275 0.053145 0.284804 1111 0.006695 0.390109 0.467033 1113 0.00931 −0.151037 −0.094238 1145 −0.003373 −0.121256 −0.288823 1161 −0.036419 −0.112814 −0.289979 1169 0.004364 −0.149179 −0.137703 1180 −0.003015 0.149485 0.243152 1181 −0.006552 0.354743 0.273738 1182 −0.063925 0.133911 −0.796733 1201 −0.024631 0.061529 −0.462534 1211 −0.0131 0.42541 0.389219 1227 0.003709 −0.172158 −0.119982 1228 −0.001968 −0.182794 −0.15988 1234 0.003295 −0.168464 −0.233929 1264 0.007382 −0.120962 −0.228059 1288 −0.025178 0.393585 0.566352 1294 0.004545 0.126708 0.283647 1308 −0.051939 −0.225136 −1.142094 1324 0.000802 0.195216 0.368476 1327 0.0232 0.29162 0.330751 1328 0.016117 −0.125314 −0.193334 1333 −0.001615 0.157104 0.160918 1334 −0.003194 0.078374 −0.585411 1352 −0.013243 −0.259131 −0.724495 1364 0.020286 −0.059623 −0.36669 1394 −0.038031 0.569499 0.281012 1400 −0.034692 −0.392913 −0.855372 1408 0.012613 0.202286 −0.410509 1421 0.015803 0.301704 −0.280571 1434 0.023441 0.24849 0.404885 1465 0.011301 1.119758 0.380817 1475 0.002495 −0.174538 −0.144746 1489 −0.005825 0.171399 0.198891 1503 −0.010846 0.33961 0.344346 1538 0.008774 0.250497 0.380736 1544 −0.001566 −0.118486 −0.225612 1565 0.003841 −0.24087 −0.188087 1586 −0.05968 0.131214 0.231979 1596 −0.012267 0.315077 0.462982 1598 −0.040336 0.405119 0.295977 1600 0.016473 0.171937 0.480309 1613 0.018672 0.639835 0.686131 1615 0.003796 −0.155045 −0.123787 1621 0.000743 0.182262 0.22026 1622 −0.01422 0.108504 0.441113 1624 −0.003494 −0.128858 −0.416283 1631 −0.066238 0.08156 0.35517 1644 0.012751 0.004567 −0.256495 1653 −0.051037 0.575903 0.659891 1666 −0.005018 0.304418 0.391773 1667 0.020618 −0.152906 −0.073514 1674 0.001052 0.230389 0.365551 1707 −0.10203 −0.508005 −0.433948 1713 −0.000033 0.227119 0.293211 1723 −0.008555 −0.013157 0.311742 1726 0.01878 −0.134004 −0.114544 1729 0.017853 0.122885 0.403719 1740 0.000129 0.082648 0.202706 1744 −0.008165 0.028902 0.157605 1754 −0.03329 0.24969 0.276391 1756 −0.006572 −0.090777 −0.187299 1764 −0.023292 0.061919 0.439367 1765 −0.069608 0.229406 −0.942888 1769 0.004735 0.111816 0.380203 1772 −0.053231 0.914364 0.703125 1784 0.011665 0.266176 0.262102 1798 0.006863 0.125618 0.179833 1802 −0.006187 −0.271892 −0.547214 1813 0.004929 0.074195 −0.38902 1822 0.008709 0.058535 0.172787 1851 −0.038706 0.176417 −0.585557 1854 0.011347 −0.148867 −0.08759 1856 0.023502 −0.039695 −0.260378 1857 0.001175 −0.00306 −0.260983 1864 −0.023131 −0.110894 −0.595764 1902 0.011275 −0.14224 −0.083923 1906 −0.018987 −0.066969 −0.26783 1910 −0.014553 −0.104128 −0.202699 1927 0.016189 0.022638 −0.210103 1936 −0.008747 −0.190402 −0.17087 1966 0.009815 −0.207021 −0.109949 1973 0.025222 0.269645 −0.254999 1997 0.000408 −0.206852 −0.093692 1998 −0.027543 −0.140155 −0.699914 2024 0.002746 0.021635 0.240366 2041 −0.006546 0.162101 0.390622 2042 0.003359 −0.068862 −0.130822 2054 0.003287 0.188219 0.311283 2056 0.017212 −0.089889 −0.160576 2059 −0.020181 1.117376 0.593213 2067 −0.034481 −0.314757 −0.571005 2069 0.020052 −0.126164 −0.092528 2084 −0.030024 0.35537 0.651561 2116 0.013573 −0.038963 −0.25063 2121 −0.071015 0.041386 −0.850915 2127 −0.042666 0.689794 0.248637 2132 −0.001535 0.140887 0.196882 2136 −0.016679 0.5014 0.158751 2148 0.007504 −0.089503 −0.424451 2162 −0.018781 −0.151041 −0.25681 2196 0.001252 −0.045446 −0.145241 2197 0.011939 0.082814 0.421803 2211 0.016656 −0.118424 −0.17814 2218 −0.001994 0.132273 0.102983 2222 −0.080043 0.129091 0.187538 2247 0.014934 −0.139989 −0.120912 2248 −0.012664 0.324801 0.485921 2259 0.009135 0.109045 −0.390417 2276 0.010096 −0.162022 −0.120129 2277 0.013334 0.571954 −0.227756 2282 0.003573 −0.28411 −0.296893 2286 −0.00426 −0.361198 −0.342302 2298 −0.042053 −0.27671 −0.589169 2302 0.008627 −0.135924 −0.184813 2310 −0.001488 −0.154965 −0.151611 2334 0.022782 0.118742 0.155021 2344 −0.046131 −0.043556 0.354686 2373 0.013698 0.020747 −0.300319 2388 −0.057599 0.240909 0.4755 2392 0.007643 −0.159192 −0.126831 2398 −0.04217 0.124478 −0.490219 2414 0.006247 0.039279 0.231344 2458 −0.047592 −0.021181 0.62265 2464 0.009492 0.497028 0.550105 2465 −0.061732 0.844778 0.746645 2474 −0.010535 0.317139 0.32638 2479 0.009625 −0.032207 −0.206553 2482 0.007713 0.134365 0.22816 2486 0.008277 −0.165135 −0.505359 2494 −0.008876 −0.013903 −0.345788 2495 0.023159 −0.11675 −0.103801 2501 0.024313 −0.133841 −0.10317 2517 0.010041 −0.026346 −0.284518 2541 0.001637 −0.123709 −0.165061 2555 0.009862 −0.295888 −0.195271 2561 0.003441 0.143297 0.393623 2563 −0.001684 −0.157035 −0.180935 2567 0.018774 0.481516 0.617251 2580 0.001717 0.072093 0.449871 2584 −0.108511 0.237285 0.358945 2591 −0.014377 0.016583 0.170925 2599 −0.004314 0.138559 −0.449886 2603 0.011638 −0.148946 −0.141157 2606 −0.008722 −0.002843 −0.263652 2612 0.006823 −0.083968 −0.181774 2627 0.033377 −0.002066 −0.307558 2631 −0.091338 −0.170022 −1.015137 2637 0.000709 −0.02223 −0.36686 2654 −0.018035 −0.080645 −0.380195 2659 0.022976 0.537017 0.816212 2664 −0.002476 −0.035144 −0.354387 2696 0.061699 0.295673 0.624181 2698 −0.008783 −0.162188 −0.319096 2699 0.021373 −0.029099 −0.143444 2700 0.004112 0.278744 0.204271 2707 0.014731 −0.005959 −0.192094 2750 0.007282 −0.224306 −0.335665 2769 −0.085357 0.275787 −0.772084 2772 0.017216 −0.120145 −0.343286 2775 −0.011673 0.769212 0.451896 2810 0.004075 −0.190069 −0.240619 2811 0.009903 −0.176453 −0.085968 2813 0.003336 0.202659 0.191714 2815 0.006303 0.092394 0.150836 2824 0.00192 −0.131874 −0.166371 2835 0.020297 −0.126422 −0.206971 2856 0.006157 −0.130875 −0.287515 2864 −0.012584 0.112957 0.202569 2865 0.002638 −0.150304 −0.265439 2868 −0.002354 0.025594 0.276877 2873 −0.003375 −0.040933 −0.559433 2891 0.012968 0.26685 0.212612 2897 −0.004267 0.32308 0.463093 2905 −0.045096 −0.397135 −0.859917 2926 −0.005235 0.098392 0.200836 2931 0.024967 0.193228 0.410268 2936 0.024484 −0.182182 −0.112346 2938 0.01805 −0.289863 −0.273244 2946 0.005996 −0.125692 −0.084214 2964 0.019559 −0.127505 −0.385534 2965 0.007544 −0.131222 −0.15763 2972 −0.062089 0.082359 0.199472 2973 0.003145 0.146062 0.413226 2976 0.007741 0.072786 −0.299474 2981 −0.018057 −0.15181 −0.335472 2995 0.012536 −0.169059 −0.090252 3004 −0.004586 0.054952 0.213188 3014 0.005466 −0.153481 −0.203641 3022 0.015475 −0.112142 −0.208532 3059 −0.014859 0.269937 0.241767 3079 −0.011007 −0.20423 −0.516356 3085 −0.007467 −0.154645 −0.263535 3094 0.009534 −0.137767 −0.14642 3105 0.023282 0.325101 0.254346 3120 0.0307 0.350781 −0.241198 3130 0.009997 −0.13136 −0.143976 3132 0.011847 −0.085343 −0.251605 3161 0.008344 −0.156984 −0.187369 3185 −0.011662 0.324166 0.476811 3194 0.002083 0.14088 0.284904 3211 0.004157 0.206272 0.386628 3214 0.025459 0.102741 0.240957 3215 0.00353 −0.064073 −0.167793 3228 0.017223 −0.161965 −0.0726 3237 0.002668 −0.009235 0.21907 3245 −0.039738 −0.344767 −0.512409 3269 −0.033522 −0.404287 −0.588228 3279 −0.059744 0.264262 0.389371 3288 −0.001709 −0.176379 −0.380142 3328 −0.001545 0.072595 0.2077 3337 0.01359 0.244776 0.208125 3338 −0.020347 −0.138845 −0.506552 3341 −0.049209 −0.011969 −0.419139 3356 0.023516 −0.13485 −0.110476 3357 0.000456 −0.135074 −0.091856 3380 −0.012204 −0.399725 −0.454969 3387 0.008267 0.330665 0.191095 3390 −0.002049 0.248303 0.32703 3395 −0.006382 −0.249059 −0.201365 3402 −0.084896 0.054938 0.463716 3416 −0.039529 −0.201668 −0.578439 3420 −0.000395 −0.09677 −0.20635 3423 0.012558 0.087882 0.242394 3426 0.01107 0.146821 −0.432986 3443 −0.015748 −0.058532 −0.400899 3444 −0.017838 0.112361 0.21707 3470 0.01235 0.202663 0.425686 3473 0.007791 0.222727 0.486992 3477 −0.007804 −0.012007 0.180183 3496 −0.078914 0.88838 0.619244 3516 −0.03045 −0.252169 −0.485051 3522 0.014247 0.255693 0.387975 3549 0.012122 1.072368 0.652041 3560 0.010452 0.067171 0.167825 3569 0.008055 0.236448 0.463364 3571 0.012994 −0.148049 −0.087744 3579 0.004924 −0.17069 −0.122234 3585 −0.001411 0.203954 0.124424 3594 0.022686 −0.159764 −0.113605 3595 0.00889 0.778268 0.724542 3627 −0.018961 −0.122255 −0.455286 3649 −0.00753 −0.075377 −0.245985 3655 −0.009543 −0.030372 0.280245 3658 0.010488 −0.100563 −0.316822 3662 −0.021261 −0.177479 −0.164925 3678 −0.018901 −0.069804 −0.40405 3689 0.008179 0.111666 0.212243 3715 0.000597 0.19448 0.237315 3720 0.006975 0.316981 −0.554667 3724 −0.006756 0.02331 −0.392742 3727 −0.023638 −0.142935 −0.651747 3749 0.01003 0.043979 0.215776 3751 0.029168 −0.073576 −0.140182 3754 0.001496 0.107186 0.165913 3755 −0.021919 0.195442 0.379175 3774 0.008601 0.081842 0.189429 3781 −0.027603 −0.124679 −0.389211 3795 −0.009508 −0.235417 −0.340756 3848 0.008156 −0.137025 −0.091425 3853 0.00189 −0.145487 −0.229147 3854 −0.009932 −0.323309 −0.627916 3865 −0.006782 0.081835 0.099887 3869 0.026028 −0.164373 −0.08952 3874 0.002977 0.004837 −0.354182 3878 −0.00536 −0.135863 −0.293698 3908 0.01371 −0.080601 −0.140019 3938 0.005563 −0.114606 −0.098469 3941 0.018012 0.177639 0.090444 3955 −0.019735 −0.159647 −0.33003

TABLE 2b progression genes SEQ ID NO log(ratio) CP log(ratio) AP log(ratio) BC 3925 0.003797 −0.153433 −0.114664

Table 3 lists the “top ten” genes that are associated with progression and response, independent of normal CD34+ expression, based on log 10 ratio of expression compared to the chronic phase pool. These genes are identified by their SEQ ID NOs in Table 3. Information for these genes is presented in Table 8.

TABLE 3 “top ten” genes SEQ ID NO log(ratio) CP log(ratio) AP log(ratio) BC REGULATION 902 0 0 0.599663 up 984 0 0 −0.77846 down 1334 0 0 −0.94289 down 1756 0 0 −0.78849 down 1813 0 0 −0.85091 down 1973 0 0 −0.79673 down 2056 0 0 −1.01514 down 2211 0 0 −0.82401 down 2561 0 0 0.686131 up 2810 0 0 −0.85992 down 2813 0 0 0.652041 up 2815 0 0 0.816212 up 2824 0 0 −1.14209 down 2864 0 0 0.651561 up 2973 0 0 0.746645 up 3085 0 0 −0.85537 down 3211 0 0 0.617251 up 3477 0 0 0.619244 up 3749 0 0 0.703125 up 3941 0 0 0.659891 up

Table 4 lists a set of 228 genes associated with imatinib resistance (the “imatinib resistance genes”). The imatinib resistance genes are identified by their SEQ ID NOs in Table 4. Information for these genes is presented in Table 8. Table 4 also listed for each gene the log ratio of expression level of the gene in samples from patients of a particular phase (e.g., CP, AP, or BC) or IM resistance (IM) versus expression level of the gene in a pool of CML bone marrow samples from chronic phase patients. Each log ratio column thus contains expression levels of markers for a particular phase or IM resistance.

TABLE 4 genes associated with imatinib resistance SEQ ID NO log(ratio) CP log(ratio) AP log(ratio) BC log(ratio) IM 20 0 0 −0.38709 0.263887 28 0 0 −0.01912 0.265124 50 0 0 0.04967 0.383703 72 0 0 −0.03184 0.248668 77 0 0 −0.1097 0.230979 91 0 0 −0.21363 0.302135 93 0 0 0.012872 0.248989 97 0 0 0.084015 0.441542 124 0 0 0.230888 0.535462 134 0 0 −0.03703 0.179006 150 0 0 −0.0693 0.172068 155 0 0 −0.13679 0.157108 171 0 0 0.196959 0.633551 195 0 0 0.02123 0.207227 243 0 0 0.11112 0.695707 254 0 0 −0.08112 0.269401 269 0 0 −0.03573 0.298949 275 0 0 −0.15251 0.212305 283 0 0 −0.03596 0.21647 292 0 0 0.20614 0.549719 342 0 0 0.208194 0.677793 371 0 0 −0.06027 0.449786 372 0 0 −0.02106 0.351234 377 0 0 −0.16901 0.161438 386 0 0 −0.07531 0.180776 406 0 0 −0.06767 0.371699 426 0 0 −0.05036 0.281576 442 0 0 −0.14473 0.198718 456 0 0 −0.05428 0.215394 459 0 0 −0.03202 0.345771 469 0 0 −0.18903 0.227286 480 0 0 0.038217 0.684655 531 0 0 −0.17195 0.414879 568 0 0 −0.06414 0.098452 622 0 0 −0.40798 0.833497 662 0 0 −0.00884 0.217496 663 0 0 −0.09438 0.107198 670 0 0 −0.17245 0.1338 709 0 0 0.187456 0.553818 722 0 0 −0.11073 0.162124 768 0 0 −0.10115 0.42413 785 0 0 0.219511 0.690758 796 0 0 −0.12656 0.145981 856 0 0 −0.01924 0.400575 880 0 0 −0.10236 0.278475 894 0 0 −0.02732 0.206984 917 0 0 −0.25561 0.212912 924 0 0 0.224269 0.708077 973 0 0 −0.01275 0.730765 977 0 0 −0.10317 0.400818 980 0 0 −0.1785 0.286644 1008 0 0 −0.10928 0.108172 1014 0 0 0.148244 0.865065 1023 0 0 0.098335 0.878985 1037 0 0 −0.33476 0.837053 1038 0 0 −0.20627 0.621468 1052 0 0 −0.2069 0.236861 1059 0 0 0.148036 0.402311 1074 0 0 −0.33264 0.239842 1089 0 0 0.174284 0.985452 1095 0 0 0.304656 0.927005 1124 0 0 −0.07093 0.616113 1143 0 0 −0.18175 0.201291 1157 0 0 −0.18174 0.21747 1170 0 0 −0.08377 0.431166 1173 0 0 −0.09515 0.560044 1182 0 0 −0.45446 0.142546 1190 0 0 0.041007 0.359776 1215 0 0 −0.06781 0.83596 1219 0 0 −0.07224 0.165806 1224 0 0 −0.05776 0.205308 1247 0 0 −0.08694 0.185421 1249 0 0 0.263515 0.605748 1267 0 0 0.263464 1.063745 1323 0 0 −0.2206 0.10102 1329 0 0 −0.00537 0.436924 1331 0 0 −0.01409 0.755256 1336 0 0 −0.15667 0.34331 1367 0 0 −0.3207 0.489696 1379 0 0 −0.17026 0.205201 1389 0 0 0.079937 0.359209 1435 0 0 0.092179 0.722108 1449 0 0 −0.467 0.171956 1451 0 0 0.425181 0.859676 1478 0 0 −0.152 0.122073 1482 0 0 0.111952 0.395553 1494 0 0 −0.16752 0.177726 1526 0 0 −0.15569 0.166092 1534 0 0 0.10057 0.802351 1549 0 0 −0.01958 0.262207 1566 0 0 −0.07228 0.314048 1591 0 0 0.253125 0.761339 1657 0 0 −0.02703 0.334287 1671 0 0 −0.13532 0.128801 1708 0 0 −0.03956 0.206351 1709 0 0 0.265264 0.510844 1731 0 0 −0.16089 0.119466 1789 0 0 −0.28125 0.246382 1820 0 0 −0.42872 0.604742 1839 0 0 −0.01985 0.652489 1840 0 0 0.057241 0.774482 1898 0 0 −0.39467 0.378527 1948 0 0 0.082745 0.793455 1949 0 0 −0.18208 0.868135 1959 0 0 −0.22455 0.344545 1965 0 0 −0.26522 0.569866 2012 0 0 −0.35247 0.31479 2033 0 0 0.040006 0.345342 2073 0 0 0.039277 0.877752 2081 0 0 −0.05539 0.149592 2087 0 0 −0.29516 0.404949 2088 0 0 −0.02581 0.326797 2106 0 0 −0.23592 0.332507 2126 0 0 −0.02439 0.515267 2145 0 0 −0.2559 0.725553 2151 0 0 −0.01135 0.414351 2172 0 0 −0.08199 0.39351 2178 0 0 −0.26619 0.102312 2181 0 0 −0.06055 0.158135 2183 0 0 0.223605 0.977949 2189 0 0 0.216936 1.068883 2199 0 0 −0.27714 0.840265 2207 0 0 −0.29681 0.440807 2228 0 0 −0.05689 0.930733 2244 0 0 −0.37335 0.576383 2269 0 0 −0.17482 0.171115 2285 0 0 −0.05323 0.923962 2286 0 0 −0.11188 0.142335 2289 0 0 −0.31747 0.354229 2292 0 0 0.437319 0.959855 2354 0 0 −0.06186 0.222863 2387 0 0 −0.60522 0.324344 2388 0 0 −0.11786 0.725499 2408 0 0 0.27178 0.449011 2427 0 0 −0.0812 0.174195 2437 0 0 0.027895 1.082811 2449 0 0 0.012028 0.297163 2479 0 0 −0.22582 0.179989 2492 0 0 −0.25009 0.349156 2531 0 0 0.07276 0.662312 2545 0 0 0.021603 0.945236 2553 0 0 −0.01276 0.395767 2564 0 0 −0.28345 0.250146 2568 0 0 −0.10977 0.19616 2582 0 0 0.253015 0.634172 2615 0 0 0.128864 1.013705 2618 0 0 −0.2905 0.559533 2629 0 0 −0.06243 0.410775 2633 0 0 −0.41692 0.392893 2652 0 0 0.205031 0.647252 2653 0 0 −0.00396 0.377357 2660 0 0 −0.53433 0.393617 2665 0 0 0.062554 0.686441 2666 0 0 0.017231 0.276612 2686 0 0 0.074055 0.352962 2697 0 0 0.142879 0.722647 2756 0 0 0.033883 0.281303 2780 0 0 −0.43199 0.457222 2802 0 0 0.032077 0.248953 2807 0 0 0.088818 0.865409 2828 0 0 0.375805 0.936957 2844 0 0 −0.10182 0.193285 2879 0 0 −0.11063 0.376181 2896 0 0 −0.12602 0.433851 2942 0 0 0.038329 0.261638 2955 0 0 0.337985 0.616413 2977 0 0 0.006318 0.640784 2980 0 0 −0.06256 0.752042 2984 0 0 −0.0839 0.535325 2989 0 0 −0.04767 0.23291 2994 0 0 −0.12413 0.24541 3004 0 0 −0.22221 0.402371 3015 0 0 −0.38468 0.767185 3040 0 0 −0.15874 0.553807 3051 0 0 −0.16014 0.258388 3095 0 0 −0.23449 0.453399 3145 0 0 0.046709 0.349592 3149 0 0 −0.07479 0.13184 3172 0 0 −0.09216 0.235379 3178 0 0 −0.16051 0.189495 3181 0 0 −0.18123 0.657828 3183 0 0 −0.08563 0.644291 3234 0 0 −0.09319 0.622993 3239 0 0 −0.15225 0.543178 3263 0 0 −0.09885 0.51508 3267 0 0 −0.0802 0.247087 3272 0 0 −0.06519 0.20193 3284 0 0 −0.39928 0.564677 3317 0 0 0.042257 0.663222 3324 0 0 −0.0387 0.202691 3334 0 0 −0.14218 0.402162 3342 0 0 0.094368 0.377785 3360 0 0 −0.18153 0.352019 3370 0 0 −0.07291 0.154629 3373 0 0 0.266208 1.01143 3378 0 0 0.154822 0.471737 3389 0 0 0.096215 0.292396 3402 0 0 0.166222 0.929501 3433 0 0 −0.08958 0.164089 3476 0 0 −0.02612 0.185903 3479 0 0 −0.23806 0.307206 3482 0 0 0.017378 0.267581 3546 0 0 0.071637 0.321201 3554 0 0 −0.10865 0.21563 3620 0 0 −0.18183 0.230787 3632 0 0 0.04804 0.247622 3677 0 0 −0.14473 0.201314 3683 0 0 0.00301 0.2633 3686 0 0 −0.03852 0.375431 3692 0 0 −0.59334 0.407906 3711 0 0 −0.07697 0.1336 3725 0 0 −0.1157 0.688963 3746 0 0 −0.09686 0.406243 3765 0 0 −0.38459 0.568063 3785 0 0 −0.02761 0.586677 3793 0 0 −0.01682 0.432956 3800 0 0 0.093978 0.693084 3804 0 0 0.149344 0.963817 3812 0 0 0.078875 0.719019 3836 0 0 0.245725 0.62927 3876 0 0 −0.10377 0.245747 3891 0 0 0.056743 0.30804 3905 0 0 −0.18947 0.77305 3935 0 0 −0.1837 0.688495 3939 0 0 −0.13203 0.177443 3946 0 0 −0.57596 0.119957 3966 0 0 −0.14854 0.290791

Tables 5a and 5b list 386 target genes, which are differentially expressed between CML blast crisis and normal immature CD34+ cells (p<0.1%) (the “target geneset”). The target genes are identified by their SEQ ID NOs in Tables 5a and 5b. Information for these genes is presented in Table 8. Table 5a lists target genes that that were not disclosed in U.S. Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003. Table 5b lists target genes that were also identified in U.S. Patent Application Publication 2003/01044026 A1, dated Jun. 5, 2003.

TABLE 5a CML target genes SEQ ID NO 2 8 51 74 88 99 105 109 116 142 146 158 174 184 185 191 204 246 252 261 267 298 309 312 321 337 343 359 365 370 379 390 393 432 444 483 490 493 494 495 503 506 522 562 564 565 571 576 596 600 602 605 607 615 628 629 631 638 644 659 664 665 675 676 688 700 701 727 728 730 741 745 759 766 781 788 790 809 813 843 840 841 845 847 873 878 884 900 902 906 908 915 934 960 962 983 1000 1012 1014 1020 1027 1036 1051 1054 1067 1089 1093 1106 1112 1132 1138 1140 1145 1158 1160 1161 1164 1165 1183 1188 1197 1202 1223 1245 1254 1288 1300 1306 1308 1311 1325 1331 1334 1346 1352 1380 1400 1409 1410 1411 1415 1416 1440 1441 1446 1452 1456 1464 1472 1489 1495 1500 1502 1503 1522 1527 1532 1534 1575 1596 1608 1614 1643 1652 1674 1689 1711 1712 1713 1724 1728 1756 1757 1762 1767 1772 1781 1785 1798 1799 1800 1802 1803 1813 1828 1849 1870 1873 1893 1910 1926 1927 1944 1990 1991 1998 2007 2011 2023 2032 2040 2042 2056 2064 2082 2085 2101 2104 2136 2161 2162 2174 2188 2200 2206 2211 2212 2213 2218 2224 2248 2252 2253 2266 2279 2304 2310 2312 2313 2320 2329 2356 2372 2388 2406 2442 2454 2462 2469 2479 2505 2525 2534 2554 2561 2563 2565 2567 2591 2600 2631 2632 2649 2654 2658 2664 2665 2670 2676 2696 2699 2721 2726 2734 2739 2766 2775 2777 2788 2810 2824 2825 2830 2842 2862 2863 2864 2892 2894 2900 2903 2921 2928 2938 2953 2964 2967 2981 3003 3019 3020 3027 3029 3047 3048 3067 3075 3085 3093 3094 3097 3103 3136 3185 3191 3194 3196 3215 3222 3238 3240 3241 3245 3248 3254 3279 3312 3329 3339 3348 3361 3364 3373 3380 3395 3396 3398 3400 3402 3428 3456 3462 3470 3500 3514 3533 3538 3555 3569 3582 3583 3611 3628 3640 3642 3646 3650 3655 3658 3685 3689 3696 3718 3755 3763 3792 3844 3845 3849 3857 3880 3901 3915 3937 3940 3955

TABLE 5b CML target genes SEQ ID NO log(ratio) BC 1776 0 3961 0

Genes that are not listed in Table 1a or 1b but which are functional equivalents of any gene listed in Table 1a or 1b can also be used with or in place of the gene listed in the table. A functional equivalent of a gene A refers to a gene that encodes a protein or mRNA that at least partially overlaps in physiological function in the cell to that of the protein or mRNA of gene A.

In various specific embodiments, different numbers and subcombinations of the genes listed in Tables 1a and/or 1b are selected as the marker set, whose profile is used in the methods of the invention, as described in Section 5.2., infra. In various embodiments, all or a subset of those genes listed in each of Tables 2a and/or 2b or Table 3, supra, or their respective functional equivalents are used.

In one embodiment, one or more genes that cluster together with one or more genes listed in a table can be selected to represent the cluster such that the marker set contains genes representing a plurality of different clusters.

In a specific embodiment, measurements of gene products of the genes, respectively, shown in Tables 2a and/or 2b, or their respective functional equivalents, are used for CML progression evaluation. In a particular embodiment, measurements of gene products of all or at least 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100 or 200 of the genes listed in Tables 2a and/or 2b are used.

In another embodiment, measurements of the gene products of the set of 20 genes shown in Table 3 (which is a subset of the genes listed in Table 2a and Table 5a) or their respective functional equivalents are used CML progression evaluation. In a particular embodiment, measurements of gene products of all or at least 5, 10, 15 or 20 of the genes listed in Table 3 are used.

In another embodiment, measurements of the gene products of the set of 10 up-regulated genes shown in Table 3 or their respective functional equivalents are used CML progression evaluation. In a particular embodiment, measurements of gene products of all or at least 5, 6, 7, 8, 9 or all 10 of the up-regulated genes listed in Table 3 are used.

In another embodiment, measurements of the gene products of the set of 10 down-regulated genes shown in Table 3 or their respective functional equivalents are used CML progression evaluation. In a particular embodiment, measurements of gene products of all or at least 5, 6, 7, 8, 9 or all 10 of the down-regulated genes listed in Table 3 are used.

In still another embodiment, measurements of the genes, respectively, shown in Table 4 or their respective functional equivalents are used for determining imatinib resistance in a patient. In a particular embodiment, measurements of gene products of all or at least 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100 or 200 of the genes listed in Table 4 are used. In a specific embodiment, imatinib resistance is determined according to the measurements of gene products of all or at least 5, 6, 7, or 8 of the genes selected from the group consisting of serine threonine kinases CTRL, MAP21K14, CLK3, MAP kinase MKNK2, the tyrosine kinase oncogene FYN, TCF7 (a putatively T cell specific transcription factor), guanine nucleotide binding proteins GNAZ and GNG11, and the MAF.

The invention also provides sets of promoter controlled genes, measurements of which can be used for evaluating the progression of CML in a patient. In one embodiment, measurements of the gene products of genes that are controlled by one or more of the promoters shown in Table 6 or their respective functional equivalents are used for evaluating CML progression. In a particular embodiment, measurements of gene products controlled by a promoter selected from the group consisting of set of promoters shown in Table 6 or their respective functional equivalents are used.

TABLE 6 Promoters associated with CML progression EXPECTA- PROMOTER P-VALUE TION SOURCE SPECIES MZF_1-4 0 0 Genes with common Homo promoter sites sapiens S8 1.22E−12 7.69E−11 Genes with common Homo promoter sites sapiens deltaEF1 5.87E−11 3.70E−09 Genes with common Homo promoter sites sapiens SPI-B 1.48E−10 9.35E−09 Genes with common Homo promoter sites sapiens Yin-Yang 1.48E−09 9.30E−08 Genes with common Homo promoter sites sapiens Ahr-ARNT 1.60E−09 1.01E−07 Genes with common Homo promoter sites sapiens MZF_5-13 1.26E−06 7.96E−05 Genes with common Homo promoter sites sapiens c-MYB_1 5.10E−06 0.000321 Genes with common Homo promoter sites sapiens

The invention provides methods for identifying a set of genes for evaluating stage/progression of CML. The methods make use of measured expression profiles of a plurality of genes (e.g., measurements of abundance levels of the corresponding gene products) in bone marrow or blood samples from a plurality of patients whose CML stage/progression status are known. As used herein, a patient is animal inflicted with CML. The patient can be but is not limited to a human, or, in a veterinary context, from non-human animals such as ruminants, horses, swine or sheep, or from domestic companion animals such as felines and canines. In one embodiment, for each of the plurality of genes a metric of correlation between expression level of the gene and survival outcome in the plurality of CML patients is determined. One or more genes are then selected based on their metrics of correlation.

Progression markers can be obtained by identifying genes whose expression levels are significantly different across CML patients of different phases of CML. In preferred embodiments, genes whose expression levels exhibit differences across different phrase groups to at least a predetermined level are selected as the genes whose expression levels correlate with CML phases. In one embodiment, the expression level differences among patients of different CML phases are evaluated using ANOVA. In one embodiment, a gene is selected if the p-value of the gene corresponds to a predetermined significance level, e.g., a p-value less than 10⁻¹¹.

The invention also provides a computer system comprising a processor, and a memory coupled to said processor and encoding one or more programs, wherein said one or more programs cause the processor to carry out a method described above.

The invention also provides a computer program product for use in conjunction with a computer having a processor and a memory connected to the processor, said computer program product comprising a computer readable storage medium having a computer program mechanism encoded thereon, wherein said computer program mechanism may be loaded into the memory of said computer and cause said computer to carry out a method described above.

5.2. Methods of Evaluating CML Progression and Responses

The invention provides methods for determining the stage or progression status in a CML patient using a measured marker profile comprising measurements of the gene products of genes, e.g., the sets of genes described in Section 5.1., supra.

5.2.1. Methods for Evaluating Progression Based On Expression Profiles

In preferred embodiments, the methods of the invention use a progression classifier, also called a classifier, for predicting CML progression and/or responsiveness to imatinib mesylate in a patient. The progression classifier can be based on any appropriate pattern recognition method that receives an input comprising a marker profile and provides an output comprising data indicating which phase the patient belongs. The progression classifier can be trained with training data from a training population of CML patients. Typically, the training data comprise for each of the CML patients in the training population a training marker profile comprising measurements of respective gene products of a plurality of genes in a suitable sample taken from the patient and CML progression information. In a preferred embodiment, the training population comprises patients from each of the different stages of CML, i.e., CP-CML, ADV-CML, or AP-CML and BC-CML. In another preferred embodiment, the training population comprises patients from each of the different IM response groups, i.e., IM resistant and IM responsive.

In preferred embodiments, the progression classifier can be based on a classification (pattern recognition) method described below, e.g., profile similarity (Section 5.2.1.1., infra); artificial neural network (Section 5.2.1.2., infra); support vector machine (SVM, Section 5.2.1.3., infra); logic regression (Section 5.2.1.4., infra), linear or quadratic discriminant analysis (Section 5.2.1.5., infra), decision trees (Section 5.2.1.6., infra), clustering (Section 5.2.1.7., infra), principal component analysis (Section 5.2.1.8., infra), nearest neighbor classifier analysis (Section 5.2.1.9., infra). Such progression classifiers can be trained with the training population using methods described in the relevant sections, infra.

The marker profile can be obtained by measuring the plurality of gene products in a CML cell sample from the patient using a method known in the art, e.g., a method described in Section 5.2.4-5.2.5., infra.

Various known statistical pattern recognition methods can be used in conjunction with the present invention. A progression classifier based on any of such methods can be constructed using the marker profiles and progression data of training patients. Such a progression classifier can then be used to evaluate the progression status of a CML patient based on the patient's marker profile. The methods can also be used to identify markers that discriminate between different progression status and/or imatinib resistance using a marker profile and progression and/or imatinib resistance data of training patients. For simplicity, the methods are often discussed with respect to evaluation of the progression status. It will be understood by a person skilled in the art that the methods are equally applicable to evaluation of IM responsiveness.

5.2.1.1. Profile Matching

A patient's CML stage or progression status can be evaluated by comparing a marker profile obtained in a suitable sample from the patient with a marker profile that is representative of a particular CML phase. Such a marker profile is also termed a “template profile” or a “template.” The degree of similarity to such a template profile provides an evaluation of the patient's CML stage or progression status. If the degree of similarity of the patient marker profile and a template profile is above a predetermined threshold, the patient is assigned a CML phase or progression status represented by the template. For example, a patient's CML stage or progression status can be evaluated by comparing a marker profile of the patient to a predetermined template profile corresponding to a certain CML stage or progression status, e.g., an ADV-CML template comprising measurements of the plurality of markers which are representative of levels of the markers in a plurality of advanced phase patients or a CP-CML template comprising measurements of the plurality of markers which are representative of levels of the markers in a plurality of chronic phase patients.

In one embodiment, the similarity is represented by a correlation coefficient between the patient's profile and the template. In one embodiment, a correlation coefficient above a correlation threshold indicates a high similarity, whereas a correlation coefficient below the threshold indicates a low similarity.

In a specific embodiment, P_(i) measures the similarity between the patient's profile {right arrow over (y)} and a template profile, e.g., a template profile comprising measurements of marker gene products representative of measurements of marker gene products of a level of progression of CML, e.g., the CP-CML template {right arrow over (z)}_(CP) or the ADV-CML template {right arrow over (z)}_(ADV). Such a coefficient, P_(i), can be calculated using the following equation: P _(i)=({right arrow over (z)} _(i) ·{right arrow over (y)})/(∥{right arrow over (z)} _(i) ∥·∥{right arrow over (y)}∥) where i designates the ith template. For example, i is CP for CP-CML template. Thus, in one embodiment, {right arrow over (y)} is classified as a CP-CML profile if P_(CP) is greater than a selected correlation threshold. In another embodiment, {right arrow over (y)} is classified as an ADV-CML profile if P_(ADV) is greater than a selected correlation threshold. In preferred embodiments, the correlation threshold is set as 0.3, 0.4, 0.5 or 0.6. In another embodiment, {right arrow over (y)} is classified as a CP-CML profile if P_(CP) is greater than P_(ADV), whereas {right arrow over (y)} is classified as a ADV-CML profile if P_(CP) is less than P_(ADV).

In another embodiment, the correlation coefficient is a weighted dot product of the patient's profile {right arrow over (y)} and a template profile, in which measurements of each different marker is assigned a weight.

In another embodiment, similarity between a patient's profile and a template is represented by a distance between the patient's profile and the template. In one embodiment, a distance below a given value indicates high similarity, whereas a distance equal to or greater than the given value indicates low similarity.

In one embodiment, the Euclidian distance according to the formula D _(i) =∥{right arrow over (y)}−{right arrow over (z)} _(i)∥ is used, where D_(i) measures the distance between the patient's profile {right arrow over (y)} and a template profile comprising measurements of marker gene products representative of measurements of marker gene products of a level of progression of CML, e.g., the CP-CML template {right arrow over (z)}_(CP), the ADV-CML template {right arrow over (z)}_(ADV) or the AP-CML template {right arrow over (z)}_(AP) or BC-CML template {right arrow over (z)}_(BC). In other embodiments, the Euclidian distance is squared to place progressively greater weight on cellular constituents that are further apart. In alternative embodiments, the distance measure D_(i) is the Manhattan distance provide by

$D_{i} = {\sum\limits_{n}{{{y(n)} - {z_{i}(n)}}}}$ where y(n) and z_(i)(n) are respectively measurements of the nth marker gene product in the patient's profile {right arrow over (y)} and a template profile.

In another embodiment, the distance is defined as D_(i)=1−P_(i), where P_(i) is the correlation coefficient or normalized dot product as described above.

In still other embodiments, the distance measure may be the Chebychev distance, the power distance, and percent disagreement, all of which are well known in the art.

A distance based similarity measure is particularly useful for classifying advanced phase CML patients as either AP-CML or BC-CML since the marker profiles of AP-CML and BC-CML differ from each other in a quantitative rather than qualitative manner. Thus, in one embodiment, the invention provides a method for classifying an advanced phase CML patient as either AP-CML or BC-CML by comparing the distances between a marker profile of the patient with an AP-CML template and a BC-CML template, and classifying the patient as either AP-CML or BC-CML if the distance to the corresponding template is smaller.

A person skilled in the art would understand that the above described methods can be applied to expression profiles of IM resistance genes for evaluation of IM responsiveness. For example, the methods can be used to compare a patient expression profile to IM resistance template and IM responsive template by calculating a P_(i) measuring the similarity between the patient's profile {right arrow over (y)} and the IM resistance template comprising measurements of marker gene products representative of measurements of marker gene products in IM resistant patients, {right arrow over (z)}_(resist), and/or IM responsive template comprising measurements of marker gene products representative of measurements of marker gene products in IM responsive patients, {right arrow over (z)}_(resp). Such a coefficient, P_(i), can be calculated using the equation described above.

5.2.1.2. Artificial Neural Network

In some embodiments, a neural network is used to classify a patient marker profile. The neural network takes the patient marker profile as an input and generates an output comprising the progression status and/or IM responsiveness. A neural network can be constructed for a selected set of molecular markers of the invention. A neural network is a two-stage regression or classification model. A neural network has a layered structure that includes a layer of input units (and the bias) connected by a layer of weights to a layer of output units. For regression, the layer of output units typically includes just one output unit. However, neural networks can handle multiple quantitative responses in a seamless fashion.

In multilayer neural networks, there are input units (input layer), hidden units (hidden layer), and output units (output layer). There is, furthermore, a single bias unit that is connected to each unit other than the input units. Neural networks are described in Duda et al., 2001, Pattern Classification, Second Edition, John Wiley & Sons, Inc., New York; and Hastie et al., 2001, The Elements of Statistical Learning, Springer-Verlag, New York.

The basic approach to the use of neural networks is to start with an untrained network, present a training pattern, e.g., marker profiles from training patients, to the input layer, and to pass signals through the net and determine the output, e.g., the status of progression and/or the status of imatinib resistance in the training patients, at the output layer. These outputs are then compared to the target values; any difference corresponds to an error. This error or criterion function is some scalar finction of the weights and is minimized when the network outputs match the desired outputs. Thus, the weights are adjusted to reduce this measure of error. For regression, this error can be sum-of-squared errors. For classification, this error can be either squared error or cross-entropy (deviation). See, e.g., Hastie et al., 2001, The Elements of Statistical Learning, Springer-Verlag, New York.

Three commonly used training protocols are stochastic, batch, and on-line. In stochastic training, patterns are chosen randomly from the training set and the network weights are updated for each pattern presentation. Multilayer nonlinear networks trained by gradient descent methods such as stochastic back-propagation perform a maximum-likelihood estimation of the weight values in the model defined by the network topology. In batch training, all patterns are presented to the network before learning takes place. Typically, in batch training, several passes are made through the training data. In online training, each pattern is presented once and only once to the net.

In some embodiments, consideration is given to starting values for weights. If the weights are near zero, then the operative part of the sigmoid commonly used in the hidden layer of a neural network (see, e.g., Hastie et al., 2001, The Elements of Statistical Learning, Springer-Verlag, New York) is roughly linear, and hence the neural network collapses into an approximately linear model. In some embodiments, starting values for weights are chosen to be random values near zero. Hence the model starts out nearly linear, and becomes nonlinear as the weights increase. Individual units localize to directions and introduce nonlinearities where needed. Use of exact zero weights leads to zero derivatives and perfect symmetry, and the algorithm never moves. Alternatively, starting with large weights often leads to poor solutions.

Since the scaling of inputs determines the effective scaling of weights in the bottom layer, it can have a large effect on the quality of the final solution. Thus, in some embodiments, at the outset all expression values are standardized to have mean zero and a standard deviation of one. This ensures all inputs are treated equally in the regularization process, and allows one to choose a meaningful range for the random starting weights. With standardization inputs, it is typical to take random uniform weights over the range [−0.7, +0.7].

A recurrent problem in the use of networks having a hidden layer is the optimal number of hidden units to use in the network. The number of inputs and outputs of a network are determined by the problem to be solved. In the present invention, the number of inputs for a given neural network can be the number of molecular markers in the selected set of molecular markers of the invention. The number of output for the neural network will typically be just one. However, in some embodiment more than one output is used so that more than just two states can be defined by the network. If too many hidden units are used in a neural network, the network will have too many degrees of freedom and is trained too long, there is a danger that the network will overfit the data. If there are too few hidden units, the training set cannot be learned. Generally speaking, however, it is better to have too many hidden units than too few. With too few hidden units, the model might not have enough flexibility to capture the nonlinearities in the data; with too many hidden units, the extra weight can be shrunk towards zero if appropriate regularization or pruning, as described below, is used. In typical embodiments, the number of hidden units is somewhere in the range of 5 to 100, with the number increasing with the number of inputs and number of training cases.

One general approach to determining the number of hidden units to use is to apply a regularization approach. In the regularization approach, a new criterion function is constructed that depends not only on the classical training error, but also on classifier complexity. Specifically, the new criterion function penalizes highly complex models; searching for the minimum in this criterion is to balance error on the training set with error on the training set plus a regularization term, which expresses constraints or desirable properties of solutions: J=J _(pat) +λJ _(reg). The parameter λ is adjusted to impose the regularization more or less strongly. In other words, larger values for λ will tend to shrink weights towards zero: typically cross-validation with a validation set is used to estimate λ. This validation set can be obtained by setting aside a random subset of the training population. Other forms of penalty can also be used, for example the weight elimination penalty (see, e.g., Hastie et al., 2001, The Elements of Statistical Learning, Springer-Verlag, New York).

Another approach to determine the number of hidden units to use is to eliminate—prune—weights that are least needed. In one approach, the weights with the smallest magnitude are eliminated (set to zero). Such magnitude-based pruning can work, but is nonoptimal; sometimes weights with small magnitudes are important for learning and training data. In some embodiments, rather than using a magnitude-based pruning approach, Wald statistics are computed. The fundamental idea in Wald Statistics is that they can be used to estimate the importance of a hidden unit (weight) in a model. Then, hidden units having the least importance are eliminated (by setting their input and output weights to zero). Two algorithms in this regard are the Optimal Brain Damage (OBD) and the Optimal Brain Surgeon (OBS) algorithms that use second-order approximation to predict how the training error depends upon a weight, and eliminate the weight that leads to the smallest increase in training error.

Optimal Brain Damage and Optimal Brain Surgeon share the same basic approach of training a network to local minimum error at weight w, and then pruning a weight that leads to the smallest increase in the training error. The predicted functional increase in the error for a change in full weight vector δw is:

${\delta\; J} = {{{\left( \frac{\partial J}{\partial w} \right)^{t} \cdot \delta}\; w} + {\frac{1}{2}\delta\;{w^{t} \cdot \frac{\partial^{2}J}{\partial w^{2}} \cdot \delta}\; w} + {O\left( {{\delta\; w}}^{3} \right)}}$ where

$\frac{\partial^{2}J}{\partial w^{2}}$ is the Hessian matrix. The first term vanishes because we are at a local minimum in error; third and higher order terms are ignored. The general solution for minimizing this function given the constraint of deleting one weight is:

${\delta\; w} = {{{- \frac{w_{q}}{\left\lbrack H^{- 1} \right\rbrack_{qq}}}{H^{- 1} \cdot u_{q}}\mspace{14mu}{and}\mspace{14mu} L_{q}} = {\frac{1}{2} - \frac{w_{q}^{2}}{\left\lbrack H^{- 1} \right\rbrack_{qq}}}}$ Here, u_(q) is the unit vector along the qth direction in weight space and L_(q) is approximation to the saliency of the weight q—the increase in training error if weight q is pruned and the other weights updated δw. These equations require the inverse of H. One method to calculate this inverse matrix is to start with a small value, H₀ ⁻¹=α⁻¹I, where α is a small parameter—effectively a weight constant. Next the matrix is updated with each pattern according to

$H_{m + 1}^{- 1} = {H_{m}^{- 1} - \frac{H_{m}^{- 1}X_{m + 1}X_{m + 1}^{T}H_{m}^{- 1}}{\frac{n}{a_{m}} + {X_{m + 1}^{T}H_{m}^{- 1}X_{m + 1}}}}$ where the subscripts correspond to the pattern being presented and α_(m) decreases with m. After the full training set has been presented, the inverse Hessian matrix is given by H⁻=H_(n) ⁻¹. In algorithmic form, the Optimal Brain Surgeon method is:

-   -   begin initialize n_(H), w, θ         -   train a reasonably large network to minimum error         -   do compute H⁻¹ by Eqn. 1

$\left. q^{*}\leftarrow{\arg\mspace{14mu}{\min\limits_{q}{{w_{q}^{2}/\left( {2\left\lbrack H^{- 1} \right\rbrack}_{qq} \right)}\left( {{saliency}\mspace{14mu} L_{q}} \right)}}} \right.$ $\left. w\leftarrow{w - {\frac{w_{q^{*}}}{\left\lbrack H^{- 1} \right\rbrack_{q^{*}q^{*}}}H^{- 1}e_{q^{*}}\mspace{14mu}\left( {{saliency}\mspace{14mu} L_{q}} \right)}} \right.$

-   -   -   until J(w)>θ

    -   return w

    -   end

The Optimal Brain Damage method is computationally simpler because the calculation of the inverse Hessian matrix in line 3 is particularly simple for a diagonal matrix. The above algorithm terminates when the error is greater than a criterion initialized to be θ. Another approach is to change line 6 to terminate when the change in J(w) due to elimination of a weight is greater than some criterion value.

In some embodiments, a back-propagation neural network (see, for example Abdi, 1994, “A neural network primer”, J. Biol System. 2, 247-283) containing a single hidden layer of ten neurons (ten hidden units) found in EasyNN-Plus version 4.0 g software package (Neural Planner Software Inc.) is used. In a specific example, parameter values within the EasyNN-Plus program are set as follows: a learning rate of 0.05, and a momentum of 0.2. In some embodiments in which the EasyNN-Plus version 4.0 g software package is used, “outlier” samples are identified by performing twenty independently-seeded trials involving 20,000 learning cycles each.

5.2.1.3. Support Vector Machine

In some embodiments of the present invention, support vector machines (SVMs) are used to classify subjects using expression profiles of marker genes described in the present invention. The SVM takes the patient marker profile as an input and generates an output comprising the progression status and/or IM responsiveness. General description of SVM can be found in, for example, Cristianini and Shawe-Taylor, 2000, An Introduction to Support Vector Machines, Cambridge University Press, Cambridge, Boser et al., 1992, “A training algorithm for optimal margin classifiers, in Proceedings of the 5^(th) Annual ACM Workshop on Computational Learning Theory, ACM Press, Pittsburgh, Pa., pp. 142-152; Vapnik, 1998, Statistical Learning Theory, Wiley, N.Y.; Duda, Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc.; Hastie, 2001, The Elements of Statistical Learning, Springer, N.Y.; and Furey et al., 2000, Bioinformatics 16, 906-914. Applications of SVM in biological applications are described in Jaakkola et al., Proceedings of the 7^(th) International Conference on Intelligent Systems for Molecular Biology, AAAI Press, Menlo Park, Calif. (1999); Brown et al., Proc. Natl. Acad. Sci. 97(1):262-67 (2000); Zien et al., Bioinformatics, 16(9):799-807 (2000); Furey et al., Bioinformatics, 16(10):906-914 (2000)

In one approach, when a SVM is used, the gene expression data is standardized to have mean zero and unit variance and the members of a training population are randomly divided into a training set and a test set. For example, in one embodiment, two thirds of the members of the training population are placed in the training set and one third of the members of the training population are placed in the test set. The expression values for a selected set of genes of the present invention is used to train the SVM. Then the ability for the trained SVM to correctly classify members in the test set is determined. In some embodiments, this computation is performed several times for a given selected set of molecular markers. In each iteration of the computation, the members of the training population are randomly assigned to the training set and the test set. Then, the quality of the combination of molecular markers is taken as the average of each such iteration of the SVM computation.

Support vector machines map a given set of binary labeled training data to a high-dimensional feature space and separate the two classes of data with a maximum margin hyperplane. In general, this hyperplane corresponds to a nonlinear decision boundary in the input space. Let XεR₀ ⊂

^(n) be the input vectors, yε{−1,+1} be the labels, and φ: R₀→F be the mapping from input space to feature space. Then the SVM learning algorithm finds a hyperplane (w,b) such that the quantity

$\gamma = {\min\limits_{i}{y_{i}\left\{ {\left\langle {w,{\phi\left( X_{i} \right)}} \right\rangle - b} \right\}}}$ is maximized, where the vector w has the same dimensionality as F, b is a real number, and γ is called the margin. The corresponding decision function is then ƒ(X)=sign(

w,φ(X)

−b)

This minimum occurs when

$w = {\sum\limits_{i}{\alpha_{i}y_{i}{\phi\left( X_{i} \right)}}}$ where {α_(i)} are positive real numbers that maximize

${\sum\limits_{i}\alpha_{i}} - {\sum\limits_{ij}{\alpha_{i}\alpha_{j}y_{i}y_{j}\left\langle {{\phi\left( X_{i} \right)},{\phi\left( X_{j} \right)}} \right\rangle}}$ subject  to ${{\sum\limits_{i}{\alpha_{i}y_{i}}} = 0},{\alpha_{i} > 0}$

The decision function can equivalently be expressed as

${f(X)} = {{sign}\left( {\sum\limits_{i}{\alpha_{i}y_{i}\left\langle {{\phi\left( {X_{i},{\phi(X)}} \right\rangle} - b} \right)}} \right.}$

From this equation it can be seen that the α_(i) associated with the training point X_(i) expresses the strength with which that point is embedded in the final decision function. A remarkable property of this alternative representation is that only a subset of the points will be associated with a non-zero α_(i). These points are called support vectors and are the points that lie closest to the separating hyperplane. The sparseness of the α vector has several computational and learning theoretic consequences. It is important to note that neither the learning algorithm nor the decision function needs to represent explicitly the image of points in the feature space, φ(X_(i)), since both use only the dot products between such images,

φ(X_(i)),φ(X_(j))

. Hence, if one were given a function K(X, Y)=

φ(X),φ(X)

, one could learn and use the maximum margin hyperplane in the feature space without ever explicitly performing the mapping. For each continuous positive definite function K(X, Y) there exists a mapping φ such that K(X, Y)=

φ(X),φ(X)

for all X, YεR₀ (Mercer's Theorem). The function K(X, Y) is called the kernel function. The use of a kernel function allows the support vector machine to operate efficiently in a nonlinear high-dimensional feature spaces without being adversely affected by the dimensionality of that space. Indeed, it is possible to work with feature spaces of infinite dimension. Moreover, Mercer's theorem makes it possible to learn in the feature space without even knowing φ and F. The matrix K_(ij)=

φ(X_(i)),φ(X_(i))

is called the kernel matrix. Finally, note that the learning algorithm is a quadratic optimization problem that has only a global optimum. The absence of local minima is a significant difference from standard pattern recognition techniques such as neural networks. For moderate sample sizes, the optimization problem can be solved with simple gradient descent techniques. In the presence of noise, the standard maximum margin algorithm described above can be subject to overfitting, and more sophisticated techniques should be used. This problem arises because the maximum margin algorithm always finds a perfectly consistent hypothesis and does not tolerate training error. Sometimes, however, it is necessary to trade some training accuracy for better predictive power. The need for tolerating training error has led to the development the soft-margin and the margin-distribution classifiers. One of these techniques replaces the kernel matrix in the training phase as follows: K←K+λI while still using the standard kernel function in the decision phase. By tuning λ, one can control the training error, and it is possible to prove that the risk of misclassifying unseen points can be decreased with a suitable choice of λ.

If instead of controlling the overall training error one wants to control the trade-off between false positives and false negatives, it is possible to modify K as follows: K←K+λD where D is a diagonal matrix whose entries are either d⁺ or d⁻, in locations corresponding to positive and negative examples. It is possible to prove that this technique is equivalent to controlling the size of the α_(i) in a way that depends on the size of the class, introducing a bias for larger α_(i) in the class with smaller d. This in turn corresponds to an asymmetric margin; i.e., the class with smaller d will be kept further away from the decision boundary. In some cases, the extreme imbalance of the two classes, along with the presence of noise, creates a situation in which points from the minority class can be easily mistaken for mislabeled points. Enforcing a strong bias against training errors in the minority class provides protection against such errors and forces the SVM to make the positive examples support vectors. Thus, choosing

$d^{+} = {{\frac{1}{n^{+}}\mspace{14mu}{and}\mspace{14mu} d^{-}} = \frac{1}{n^{-}}}$ provides a heuristic way to automatically adjust the relative importance of the two classes, based on their respective cardinalities. This technique effectively controls the trade-off between sensitivity and specificity.

In the present invention, a linear kernel can be used. The similarity between two marker profiles X and Y can be the dot product X·Y. In one embodiment, the kernel is K(X,Y)=X·Y+1

In another embodiment, a kernel of degree d is used

-   -   K(X, Y)=(X·Y+1)^(d), where d can be either 2, 3, . . . .

In still another embodiment, a Gaussian kernel is used

${K\left( {X,Y} \right)} = {\exp\left( \frac{- {{X - Y}}^{2}}{2\sigma^{2}} \right)}$

where σ is the width of the Gaussian.

5.2.1.4. Logistic Regression

In some embodiments, the progression classifier is based on a regression model, preferably a logistic regression model. Such a regression model includes a coefficient for each of the molecular markers in a selected set of molecular markers of the invention. In such embodiments, the coefficients for the regression model are computed using, for example, a maximum likelihood approach. In particular embodiments, molecular marker data from two different clinical groups, e.g., chronic phase and advanced phase or imatinib resistant and imatinib sensitive, is used and the dependent variable is the clinical status of the patient for which molecular marker characteristic data are from.

Some embodiments of the present invention provide generalizations of the logistic regression model that handle multicategory (polychotomous) responses. Such embodiments can be used to discriminate an organism into one or three or more clinical groups, e.g., chronic phase, accelerated phase, and blast phase. Such regression models use multicategory logit models that simultaneously refer to all pairs of categories, and describe the odds of response in one category instead of another. Once the model specifies logits for a certain (J−1) pairs of categories, the rest are redundant. See, for example, Agresti, An Introduction to Categorical Data Analysis, John Wiley & Sons, Inc., 1996, New York, Chapter 8, which is hereby incorporated by reference.

5.2.1.5. Discriminant Analysis

Linear discriminant analysis (LDA) attempts to classify a subject into one of two categories based on certain object properties. In other words, LDA tests whether object attributes measured in an experiment predict categorization of the objects. LDA typically requires continuous independent variables and a dichotomous categorical dependent variable. In the present invention, the expression values for the selected set of molecular markers of the invention across a subset of the training population serve as the requisite continuous independent variables. The clinical group classification of each of the members of the training population serves as the dichotomous categorical dependent variable.

LDA seeks the linear combination of variables that maximizes the ratio of between-group variance and within-group variance by using the grouping information. Implicitly, the linear weights used by LDA depend on how the expression of a molecular marker across the training set separates in the two groups (e.g., a group that has CP-CML and a group that have ADV-CMP) and how this gene expression correlates with the expression of other genes. In some embodiments, LDA is applied to the data matrix of the N members in the training sample by K genes in a combination of genes described in the present invention. Then, the linear discriminant of each member of the training population is plotted. Ideally, those members of the training population representing a first subgroup (e.g. those subjects that have CP-CML) will cluster into one range of linear discriminant values (e.g., negative) and those member of the training population representing a second subgroup (e.g. those subjects that have ADV-CML) will cluster into a second range of linear discriminant values (e.g., positive). The LDA is considered more successful when the separation between the clusters of discriminant values is larger. For more information on linear discriminant analysis, see Duda, Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc; and Hastie, 2001, The Elements of Statistical Learning, Springer, N.Y.; Venables & Ripley, 1997, Modern Applied Statistics with s-plus, Springer, N.Y.

Quadratic discriminant analysis (QDA) takes the same input parameters and returns the same results as LDA. QDA uses quadratic equations, rather than linear equations, to produce results. LDA and QDA are interchangeable, and which to use is a matter of preference and/or availability of software to support the analysis. Logistic regression takes the same input parameters and returns the same results as LDA and QDA.

5.2.1.6. Decision Trees

In some embodiments of the present invention, decision trees are used to classify patients using expression data for a selected set of molecular markers of the invention. Decision tree algorithms belong to the class of supervised learning algorithms. The aim of a decision tree is to induce a classifier (a tree) from real-world example data. This tree can be used to classify unseen examples which have not been used to derive the decision tree.

A decision tree is derived from training data. An example contains values for the different attributes and what class the example belongs. In one embodiment, the training data is expression data for a combination of genes described in the present invention across the training population.

The following algorithm describes a decision tree derivation:

Tree(Examples,Class,Attributes)

Create a root node

If all Examples have the same Class value, give the root this label

Else if Attributes is empty label the root according to the most common value

Else begin

-   -   Calculate the information gain for each attribute     -   Select the attribute A with highest information gain and make         this the root attribute     -   For each possible value, v, of this attribute         -   Add a new branch below the root, corresponding to A=v         -   Let Examples(v) be those examples with A=v         -   If Examples(v) is empty, make the new branch a leaf node             labeled with the most common value among Examples         -   Else let the new branch be the tree created by             -   Tree(Examples(v),Class,Attributes—{A}) end                 A more detailed description of the calculation of                 information gain is shown in the following. If the                 possible classes v_(i); of the examples have                 probabilities P(v_(i)) then the information content I of                 the actual answer is given by:

${I\left( {{P\left( v_{1} \right)},\ldots\mspace{11mu},{P\left( v_{n} \right)}} \right)} = {\sum\limits_{i = 1}^{n}{{- {P\left( v_{i} \right)}}\log_{2}{P\left( v_{i} \right)}}}$ The I-value shows how much information we need in order to be able to describe the outcome of a classification for the specific dataset used. Supposing that the dataset contains p positive (e.g. has ADV-CML) and n negative (e.g. has CP-CML) examples (e.g. individuals), the information contained in a correct answer is:

${I\left( {\frac{p}{p + n},\frac{n}{p + n}} \right)} = {{{- \frac{p}{p + n}}\log_{2}\frac{p}{p + n}} - {\frac{n}{p + n}\log_{2}\frac{n}{p + n}}}$ where log₂ is the logarithm using base two. By testing single attributes the amount of information needed to make a correct classification can be reduced. The remainder for a specific attribute A (e.g. a gene) shows how much the information that is needed can be reduced.

${{Remainder}\mspace{14mu}(A)} = {\sum\limits_{i = 1}^{v}{\frac{p_{i} + n_{i}}{p + n}{I\left( {\frac{p_{i}}{p_{i} + n_{i}},\frac{n_{i}}{p_{i} + n_{i}}} \right)}}}$ “v” is the number of unique attribute values for attribute A in a certain dataset, “i” is a certain attribute value, “p_(i)” is the number of examples for attribute A where the classification is positive (e.g. cancer), “n_(i)” is the number of examples for attribute A where the classification is negative (e.g. healthy).

The information gain of a specific attribute A is calculated as the difference between the information content for the classes and the remainder of attribute A:

${{Gain}\mspace{14mu}(A)} = {{I\left( {\frac{p}{p + n},\frac{n}{p + n}} \right)} - {{Remainder}\mspace{14mu}(A)}}$ The information gain is used to evaluate how important the different attributes are for the classification (how well they split up the examples), and the attribute with the highest information.

In general there are a number of different decision tree algorithms, many of which are described in Duda, Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc. Decision tree algorithms often require consideration of feature processing, impurity measure, stopping criterion, and pruning. Specific decision tree algorithms include, cut are not limited to classification and regression trees (CART), multivariate decision trees, ID3, and C4.5.

In one approach, when an exemplary embodiment of a decision tree is used, the gene expression data for a selected set of molecular markers of the invention across a training population is standardized to have mean zero and unit variance. The members of the training population are randomly divided into a training set and a test set. For example, in one embodiment, two thirds of the members of the training population are placed in the training set and one third of the members of the training population are placed in the test set. The expression values for a select combination of genes described in the present invention is used to construct the decision tree. Then, the ability for the decision tree to correctly classify members in the test set is determined. In some embodiments, this computation is performed several times for a given combination of molecular markers. In each iteration of the computation, the members of the training population are randomly assigned to the training set and the test set. Then, the quality of the combination of molecular markers is taken as the average of each such iteration of the decision tree computation.

5.2.1.7. Clustering

In some embodiments, the expression values for a selected set of molecular markers of the invention are used to cluster a training set. For example, consider the case in which ten genes described in the present invention are used. Each member m of the training population will have expression values for each of the ten genes. Such values from a member m in the training population define the vector:

X_(1m) X_(2m) X_(3m) X_(4m) X_(5m) X_(6m) X_(7m) X_(8m) X_(9m) X_(10m) where X_(im) is the expression level of the i^(th) gene in organism m. If there are m organisms in the training set, selection of i genes will define m vectors. Note that the methods of the present invention do not require that each the expression value of every single gene used in the vectors be represented in every single vector m. In other words, data from a subject in which one of the i^(th) genes is not found can still be used for clustering. In such instances, the missing expression value is assigned either a “zero” or some other normalized value. In some embodiments, prior to clustering, the gene expression values are normalized to have a mean value of zero and unit variance.

Those members of the training population that exhibit similar expression patterns across the training group will tend to cluster together. A particular combination of genes of the present invention is considered to be a good classifier in this aspect of the invention when the vectors cluster into the trait groups found in the training population. For instance, if the training population includes patients with chronic phase and advanced phase CML, a clustering classifier will cluster the population into two groups, with each group uniquely representing either chronic phase or advanced phase.

Clustering is described on pages 211-256 of Duda and Hart, Pattern Classification and Scene Analysis, 1973, John Wiley & Sons, Inc., New York. As described in Section 6.7 of Duda, the clustering problem is described as one of finding natural groupings in a dataset. To identify natural groupings, two issues are addressed. First, a way to measure similarity (or dissimilarity) between two samples is determined. This metric (similarity measure) is used to ensure that the samples in one cluster are more like one another than they are to samples in other clusters. Second, a mechanism for partitioning the data into clusters using the similarity measure is determined.

Similarity measures are discussed in Section 6.7 of Duda, where it is stated that one way to begin a clustering investigation is to define a distance function and to compute the matrix of distances between all pairs of samples in a dataset. If distance is a good measure of similarity, then the distance between samples in the same cluster will be significantly less than the distance between samples in different clusters. However, as stated on page 215 of Duda, clustering does not require the use of a distance metric. For example, a nonmetric similarity ftmction s(x, x′) can be used to compare two vectors x and x′. Conventionally, s(x, x′) is a symmetric function whose value is large when x and x′ are somehow “similar”. An example of a nonmetric similarity function s(x, x′) is provided on page 216 of Duda.

Once a method for measuring “similarity” or “dissimilarity” between points in a dataset has been selected, clustering requires a criterion function that measures the clustering quality of any partition of the data. Partitions of the data set that extremize the criterion function are used to cluster the data. See page 217 of Duda. Criterion functions are discussed in Section 6.8 of Duda.

More recently, Duda et al., Pattern Classification, 2^(nd) edition, John Wiley & Sons, Inc. New York, has been published. Pages 537-563 describe clustering in detail. More information on clustering techniques can be found in Kaufman and Rousseeuw, 1990, Finding Groups in Data: An Introduction to Cluster Analysis, Wiley, New York, N.Y.; Everitt, 1993, Cluster analysis (3d ed.), Wiley, New York, N.Y.; and Backer, 1995, Computer-Assisted Reasoning in Cluster Analysis, Prentice Hall, Upper Saddle River, N.J. Particular exemplary clustering techniques that can be used in the present invention include, but are not limited to, hierarchical clustering (agglomerative clustering using nearest-neighbor algorithm, farthest-neighbor algorithm, the average linkage algorithm, the centroid algorithm, or the sum-of-squares algorithm), k-means clustering, fuzzy k-means clustering algorithm, and Jarvis-Patrick clustering.

5.2.1.8. Principal Component Analysis

Principal component analysis (PCA) has been proposed to analyze gene expression data. Principal component analysis is a classical technique to reduce the dimensionality of a data set by transforming the data to a new set of variable (principal components) that summarize the features of the data. See, for example, Jolliffe, 1986, Principal Component Analysis, Springer, N.Y. Principal components (PCs) are uncorrelate and are ordered such that the k^(th) PC has the kth largest variance among PCs. The k^(th) PC can be interpreted as the direction that maximizes the variation of the projections of the data points such that it is orthogonal to the first k−1 PCs. The first few PCs capture most of the variation in the data set. In contrast, the last few PCs are often assumed to capture only the residual ‘noise’ in the data.

PCA can also be used to create a progression classifier in accordance with the present invention. In such an approach, vectors for a selected set of molecular markers of the invention can be constructed in the same manner described for clustering above. In fact, the set of vectors, where each vector represents the expression values for the select genes from a particular member of the training population, can be considered a matrix. In some embodiments, this matrix is represented in a Free-Wilson method of qualitative binary description of monomers (Kubinyi, 1990, 3D QSAR in drug design theory methods and applications, Pergamon Press, Oxford, pp 589-638), and distributed in a maximally compressed space using PCA so that the first principal component (PC) captures the largest amount of variance information possible, the second principal component (PC) captures the second largest amount of all variance information, and so forth until all variance information in the matrix has been accounted for.

Then, each of the vectors (where each vector represents a member of the training population) is plotted. Many different types of plots are possible. In some embodiments, a one-dimensional plot is made. In this one-dimensional plot, the value for the first principal component from each of the members of the training population is plotted. In this form of plot, the expectation is that members of a first group (e.g. chronic phase patients) will cluster in one range of first principal component values and members of a second group (e.g., advance phase patients) will cluster in a second range of first principal component values.

In one example, the training population comprises two groups: chronic phase patients and advanced phase patients or imatinib resistant and imatinib sensitive. The first principal component is computed using the molecular marker expression values for the select genes of the present invention across the entire training population data set. Then, each member of the training set is plotted as a function of the value for the first principal component. In this example, those members of the training population in which the first principal component is positive are the chronic phase (or imatinib sensitive) patients and those members of the training population in which the first principal component is negative are advanced phase (or imatinib resistant) patients.

In some embodiments, the members of the training population are plotted against more than one principal component. For example, in some embodiments, the members of the training population are plotted on a two-dimensional plot in which the first dimension is the first principal component and the second dimension is the second principal component. In such a two-dimensional plot, the expectation is that members of each subgroup represented in the training population will cluster into discrete groups. For example, a first cluster of members in the two-dimensional plot will represent subjects with CP-CML, a second cluster of members in the two-dimensional plot will represent subjects with ADV-CML, and so forth.

In some embodiments, the members of the training population are plotted against more than two principal components and a determination is made as to whether the members of the training population are clustering into groups that each uniquely represents a subgroup found in the training population. In some embodiments, principal component analysis is performed by using the R mva package (Anderson, 1973, Cluster Analysis for applications, Academic Press, New York 1973; Gordon, Classification, Second Edition, Chapman and Hall, CRC, 1999.). Principal component analysis is further described in Duda, Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc.

5.2.1.9. Nearest Neighbor Classifier Analysis

Nearest neighbor classifiers are memory-based and require no model to be fit. Given a query point x₀, the k training points x_((r)), r, . . . , k closest in distance to x₀ are identified and then the point x₀ is classified using the k nearest neighbors. Ties can be broken at random. In some embodiments, Euclidean distance in feature space is used to determine distance as: d _((i)) =∥x _((i)) −x ₀∥. Typically, when the nearest neighbor algorithm is used, the expression data used to compute the linear discriminant is standardized to have mean zero and variance 1. In the present invention, the members of the training population are randomly divided into a training set and a test set. For example, in one embodiment, two thirds of the members of the training population are placed in the training set and one third of the members of the training population are placed in the test set. Profiles of a selected set of molecular markers of the invention represents the feature space into which members of the test set are plotted. Next, the ability of the training set to correctly characterize the members of the test set is computed. In some embodiments, nearest neighbor computation is performed several times for a given combination of genes of the present invention. In each iteration of the computation, the members of the training population are randomly assigned to the training set and the test set. Then, the quality of the combination of genes is taken as the average of each such iteration of the nearest neighbor computation.

The nearest neighbor rule can be refined to deal with issues of unequal class priors, differential misclassification costs, and feature selection. Many of these refinements involve some form of weighted voting for the neighbors. For more information on nearest neighbor analysis, see Duda, Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc; and Hastie, 2001, The Elements of Statistical Learning, Springer, N.Y.

5.2.1.10. Evolutionary Methods

Inspired by the process of biological evolution, evolutionary methods of classifier design employ a stochastic search for an optimal classifier. In broad overview, such methods create several classifiers—a population—from measurements of gene products of the present invention. Each classifier varies somewhat from the other. Next, the classifiers are scored on expression data across the training population. In keeping with the analogy with biological evolution, the resulting (scalar) score is sometimes called the fitness. The classifiers are ranked according to their score and the best classifiers are retained (some portion of the total population of classifiers). Again, in keeping with biological terminology, this is called survival of the fittest. The classifiers are stochastically altered in the next generation—the children or offspring. Some offspring classifiers will have higher scores than their parent in the previous generation, some will have lower scores. The overall process is then repeated for the subsequent generation: The classifiers are scored and the best ones are retained, randomly altered to give yet another generation, and so on. In part, because of the ranking, each generation has, on average, a slightly higher score than the previous one. The process is halted when the single best classifier in a generation has a score that exceeds a desired criterion value. More information on evolutionary methods is found in, for example, Duda, Pattern Classification, Second Edition, 2001, John Wiley & Sons, Inc.

5.2.1.11. Bagging, Boosting and the Random Subspace Method

Bagging, boosting and the random subspace method are combining techniques that can be used to improve weak classifiers. These techniques are designed for, and usually applied to, decision trees. In addition, Skurichina and Duin provide evidence to suggest that such techniques can also be useful in linear discriminant analysis.

In bagging, one samples the training set, generating random independent bootstrap replicates, constructs the classifier on each of these, and aggregates them by a simple majority vote in the final decision rule. See, for example, Breiman, 1996, Machine Learning 24, 123-140; and Efron & Tibshirani, An Introduction to Bootstrap, Chapman & Hall, New York, 1993.

In boosting, classifiers are constructed on weighted versions of the training set, which are dependent on previous classification results. Initially, all objects have equal weights, and the first classifier is constructed on this data set. Then, weights are changed according to the performance of the classifier. Erroneously classified objects (molecular markers in the data set) get larger weights, and the next classifier is boosted on the reweighted training set. In this way, a sequence of training sets and classifiers is obtained, which is then combined by simple majority voting or by weighted majority voting in the final decision. See, for example, Freund & Schapire, “Experiments with a new boosting algorithm,” Proceedings 13^(th) International Conference on Machine Learning, 1996, 148-156.

To illustrate boosting, consider the case where there are two phenotypic groups exhibited by the population under study, phenotype 1 (e.g., advanced phase patients), and phenotype 2 (e.g., chronic phase patients). Given a vector of molecular markers X, a classifier G(X) produces a prediction taking one of the type values in the two value set: {phenotype 1, phenotype 2}. The error rate on the training sample is

$\overset{\_}{err} = {\frac{1}{N}{\sum\limits_{i = 1}^{N}{I\left( {y_{i} \neq {G\left( x_{i} \right)}} \right)}}}$ where N is the number of subjects in the training set (the sum total of the subjects that have either phenotype 1 or phenotype 2).

A weak classifier is one whose error rate is only slightly better than random guessing. In the boosting algorithm, the weak classification algorithm is repeatedly applied to modified versions of the data, thereby producing a sequence of weak classifiers G_(m)(x), m=1, 2, . . . , M. The predictions from all of the classifiers in this sequence are then combined through a weighted majority vote to produce the final prediction:

${G(x)} = {{sign}\mspace{11mu}\left( {\sum\limits_{m = 1}^{M}{\alpha_{m}{G_{m}(x)}}} \right)}$ Here α₁, α₂, . . . , α_(M) are computed by the boosting algorithm and their purpose is to weigh the contribution of each respective G_(m)(x). Their effect is to give higher influence to the more accurate classifiers in the sequence.

The data modifications at each boosting step consist of applying weights w₁, w₂, . . . , w_(n) to each of the training observations (x_(i), y_(i)), i=1, 2, . . . , N. Initially all the weights are set to w_(i)=1/N, so that the first step simply trains the classifier on the data in the usual manner. For each successive iteration m=2, 3, . . . , M the observation weights are individually modified and the classification algorithm is reapplied to the weighted observations. At stem m, those observations that were misclassified by the classifier G_(m−1)(x) induced at the previous step have their weights increased, whereas the weights are decreased for those that were classified correctly. Thus as iterations proceed, observations that are difficult to correctly classify receive ever-increasing influence. Each successive classifier is thereby forced to concentrate on those training observations that are missed by previous ones in the sequence.

The exemplary boosting algorithm is summarized as follows:

1. Initialize the observation weights w_(i)=1/N, i=1, 2, . . . , N.

2. For m=1 to M:

-   -   (a) Fit a classifier G_(m)(x) to the training set using weights         w_(i).     -   (b) Compute

${err}_{m} = \frac{\sum\limits_{i = 1}^{N}{w_{i}{I\left( {y_{i} \neq {G_{m}\left( x_{i} \right)}} \right)}}}{\sum\limits_{i = 1}^{N}w_{i}}$

-   -   (c) Compute α_(m)=log((1−err_(m))/err_(m)).     -   (d) Set w_(i)←w_(i)·exp[α_(m)·I(y_(i)≠G_(m)(x_(i)))], i=1, 2, .         . . , N.

${3.\mspace{14mu}{Output}\mspace{14mu}{G(x)}} = {{sign}\mspace{14mu}\left\lfloor {\sum\limits_{m = 1}^{M}\;{\alpha_{m}{G_{m}(x)}}} \right\rfloor}$ In the algorithm, the current classifier G_(m)(x) is induced on the weighted observations at line 2a. The resulting weighted error rate is computed at line 2b. Line 2c calculates the weight α_(m) given to G_(m)(x) in producing the final classifier G(x) (line 3). The individual weights of each of the observations are updated for the next iteration at line 2d. Observations misclassified by G_(m)(x) have their weights scaled by a factor exp(α_(m)), increasing their relative influence for inducing the next classifier G_(m+1)(x) in the sequence. In some embodiments, modifications of the Freund and Schapire, 1997, Journal of Computer and System Sciences 55, pp. 119-139, boosting method are used. See, for example, Hasti et al., The Elements of Statistical Learning, 2001, Springer, N.Y., Chapter 10. In some embodiments, boosting or adaptive boosting methods are used.

In some embodiments, modifications of Freund and Schapire, 1997, Journal of Computer and System Sciences 55, pp. 119-139, are used. For example, in some embodiments, feature preselection is performed using a technique such as the nonparametric scoring methods of Park et al., 2002, Pac. Symp. Biocomput. 6, 52-63. Feature preselection is a form of dimensionality reduction in which the genes that discriminate between classifications the best are selected for use in the classifier. Then, the LogitBoost procedure introduced by Friedman et al., 2000, Ann Stat 28, 337-407 is used rather than the boosting procedure of Freund and Schapire. In some embodiments, the boosting and other classification methods of Ben-Dor et al., 2000, Journal of Computational Biology 7, 559-583 are used in the present invention. In some embodiments, the boosting and other classification methods of Freund and Schapire, 1997, Journal of Computer and System Sciences 55, 119-139, are used.

In the random subspace method, classifiers are constructed in random subspaces of the data feature space. These classifiers are usually combined by simple majority voting in the final decision rule. See, for example, Ho, “The Random subspace method for constructing decision forests,” IEEE Trans Pattern Analysis and Machine Intelligence, 1998; 20(8): 832-844.

5.2.1.12. Other Algorithms

The pattern classification and statistical techniques described above are merely examples of the types of models that can be used to construct a model for classification. Moreover, combinations of the techniques described above can be used. Some combinations, such as the use of the combination of decision trees and boosting, have been described. However, many other combinations are possible. In addition, in other techniques in the art such as Projection Pursuit and Weighted Voting can be used to construct a progression classifier.

5.2.2. Methods of Determining Aberrant Regulation of CML Target Genes

The invention also provides methods and compositions for determining aberrant regulation in CML target genes and/or their encoded proteins. Such information can be used to determine a treatment regimen for a patient. For example, patients who have a defective regulation of a CML target gene can be identified. A treatment regimen including a therapy to regulate the gene can be prescribed to the patient. Thus, the invention provides methods and composition for assigning treatment regimen for a cancer patient. The invention also provides methods and composition for monitoring treatment progress for a CML patient based on the status of one or more of the CML target proteins.

A variety of methods can be employed for the diagnostic and prognostic evaluation of patients for their status of CML target genes or proteins. In one embodiment, measurements of expression level of one or more of the CML target genes listed in Tables 5a and 5b, and/or abundance or activity level the encoded proteins are used. One or more of these genes or proteins having a level of expression or activity deviated from a respective predetermined threshold indicate aberrant regulation of the genes or proteins.

In one embodiment, the method comprises determining an expression level of a CML target gene (a gene listed in Table 5a or 5b) in the sample of a patient, and determining whether the expression level is deviated (above or below) a predetermined threshold, and the expression level deviated from a predetermined threshold level indicates aberrant regulation of the gene in the patient. Preferably, the predetermined threshold level is at least 2-fold, 4-fold, 8-fold, or 10-fold of the normal expression level of an aberrantly up-regulated CML target gene or less than 50%, 25%, 10% or 1% of the normal level of an aberrantly down-regulated CML target gene. In another embodiment, the method comprises determining a level of abundance of a CML target protein, i.e., a protein encoded by a CML target gene, in a sample from a patient, and determining whether the level of abundance is deviated a predetermined threshold, and a level of abundance of the protein deviated from a predetermined threshold level indicates aberrant regulation of the protein in the patient. In still another embodiment, the method comprises determining a level of activity of a protein encoded by the CML target gene in a sample of a patient, and determining whether the level of activity is deviated a predetermined threshold, and an activity level deviated from a predetermined threshold level indicates aberrant regulation of the protein in the patient. A reduced activity may be a result of mutation of the CML target gene. Thus, the invention also provides a method for evaluating the status of CML target in a patient, comprising determining a mutation in a CML target gene or a protein encoded by the CML target gene in a sample from the patient, and the detection of a mutation causing the activity of the CML target protein to deviate from a predetermined threshold level indicates aberrant regulation of the protein in the patient. Preferably, the predetermined threshold level of abundance or activity is at least 2-fold, 4-fold, 8-fold, or 10-fold above the normal level of abundance or activity of an aberrantly up-regulated CML target protein or less than 50%, 25%, 10% or 1% of the normal level of an aberrantly down-regulated CML target protein. In the foregoing embodiments, and the embodiments described below, the sample can be an ex vivo cell sample, e.g., cells in a cell culture, or in vivo cells.

In a specific embodiment, the method comprises determining an expression level of a CML target gene selected from the group consisting of the up-regulated genes listed in Table 3 (which is a subset of the genes listed in Table 5a) in the sample of a patient, and determining whether the expression level is above a predetermined threshold, and an expression level above a predetermined threshold level indicates aberrant regulation of the gene in the patient. Preferably, the predetermined threshold level is at least 2-fold, 4-fold, 8-fold, or 10-fold of the normal expression level of the gene. In another embodiment, the method comprises determining a level of abundance of a protein encoded by a gene selected from the group consisting of the up-regulated genes listed in Table 3 in a sample from a patient, and determining whether the level is above a predetermined threshold, and a level of abundance of the protein above a predetermined threshold level indicates aberrant regulation of the protein in the patient.

In another specific embodiment, the method comprises determining an expression level of a CML target gene selected from the group consisting of the down-regulated genes listed in Table 3 in the sample of a patient, and determining whether the expression level is below a predetermined threshold, and an expression level below a predetermined threshold level indicates aberrant regulation of the gene in the patient. Preferably, the predetermined threshold level is a level less than 50%, 25%, 10% or 1% of the normal expression level of the gene. In another embodiment, the method comprises determining a level of abundance of a protein encoded by a gene selected from the group consisting of the down-regulated genes listed in Table 3 in a sample from a patient, and determining whether the level is below a predetermined threshold, and a level of abundance of the protein below a predetermined threshold level indicates aberrant regulation of the protein in the patient.

In one embodiment, the method comprises determining an expression level of an imatinib resistance gene (a gene listed in Table 4) in the sample of a patient, and determining whether the expression level is deviated (above or below) a predetermined threshold, and an expression level deviated from a predetermined threshold level indicates that the patient is resistant to imatinib treatment. Preferably, the predetermined threshold level is at least 2-fold, 4-fold, 8-fold, or 10-fold of the normal expression level of an aberrantly up-regulated imatinib resistance gene or less than 50%, 25%, 10% or 1% of the normal level of an aberrantly down-regulated imatinib resistance gene. In another embodiment, the method comprises determining a level of abundance of an imatinib resistance protein, i.e., a protein encoded by an imatinib resistance gene, in a sample from a patient, and determining whether the level is deviated (above or below) a predetermined threshold, and a level of abundance of the protein deviated from a predetermined threshold level indicates that the patient is resistant to imatinib treatment. In still another embodiment, the method comprises determining a level of activity of a protein encoded by an imatinib resistance gene in a sample of a patient, and determining whether the level is deviated (above or below) a predetermined threshold, and an activity level deviated from a predetermined threshold level indicates that the patient is resistant to imatinib treatment. Such reduce activity may be a result of mutation of the imatinib resistance gene. Thus, the invention also provides a method for evaluating imatinib resistance in a patient, comprising determining a mutation in an imatinib resistance gene or a protein encoded by the imatinib resistance gene in a sample from the patient, and the detection of a mutation causing the activity of the imatinib resistance protein to deviate from a predetermined threshold level indicates the patient is resistant to imatinib treatment. Preferably, the predetermined threshold level of abundance or activity is at least 2-fold, 4-fold, 8-fold, or 10-fold above the normal level of abundance or activity of an aberrantly up-regulated imatinib resistance protein or less than 50%, 25%, 10% or 1% of the nomal level of an aberrantly down-regulated imatinib resistance protein.

In a specific embodiment, imatinib resistance is determined according to the expression levels of one or more genes selected from the group consisting of serine threonine kinases CTRL, MAP21K14, CLK3, MAP kinase MKNK2, the tyrosine kinase oncogene FYN, TCF7 (a putatively T cell specific transcription factor), guanine nucleotide binding proteins GNAZ and GNG11, and the MAF.

Such methods may, for example, utilize reagents such as nucleotide sequences and antibodies, e.g., the CML progression nucleotide sequences, and antibodies directed against CML progression proteins, including peptide fragments thereof. Specifically, such reagents may be used, for example, for: (1) the detection of the presence of mutations in a CML progression gene, or the detection of either over- or under-expression of a CML progression gene relative to the normal expression level; and (2) the detection of either an over- or an under-abundance of a CML progression protein relative to the normal CML progression protein level. These methods are also applicable to imatinib resistance genes and/or proteins.

The methods described herein may be performed, for example, by utilizing pre-packaged diagnostic kits comprising nucleic acid of at least one specific CML progression gene or an antibody that binds a CML progression/target protein or an IM resistance protein described herein, which may be conveniently used, e.g., in clinical settings, to diagnose patients exhibiting CML progression/target protein related disorder or abnormalities or exhibiting IM resistance.

For the detection of mutations in a CML progression/target gene or an IM resistance gene, any nucleated cell can be used as a starting source for genomic nucleic acid, e.g., bone marrow or peripheral blood. For the detection of expression of a CML progression/target gene or an IM resistance gene or CML progression/target gene or IM resistance gene products, any cell type or tissue in which the CML progression/target gene or the IM resistance gene is expressed may be utilized.

Nucleic acid-based detection techniques and peptide detection techniques are described in Section 5.3., infra. In one embodiment, the expression levels of one or more marker genes are measured using qRT-PCR.

5.2.3. Methods of Detecting CML Cells

The invention also provides diagnostic methods for the detection of CML cells, e.g., advanced phase CML hematopoetic stem cells and/or immature myeloid cells, by detecting a cell surface expressed CML progression protein (e.g., PRAME or CD47) or conserved variants or peptide fragments thereof, using, for example, immunoassays wherein the CML progression protein or conserved variants or peptide fragments are detected by their interaction with an anti-CML progression protein antibody.

For example, antibodies, or fragments of antibodies, such as those described in the present invention may be used to quantitatively or qualitatively detect advanced phase CML hematopoetic stem cells and/or immature myeloid cells by the presence of a CML progression protein or conserved variants or peptide fragments thereof on their surfaces. This can be accomplished, for example, by immunofluorescence techniques employing a fluorescently labeled antibody (see below, this Section) coupled with light microscopic, flow cytometric, or fluorimetric detection.

The antibodies (or fragments thereof) useful in the present invention may, additionally, be employed histologically, as in immunofluorescence or immunoelectron microscopy, for in situ detection of a CML progression protein or conserved variants or peptide fragments thereof. In situ detection may be accomplished by removing a histological specimen from a patient, e.g., bone marrow, and applying thereto a labeled antibody of the present invention. The antibody (or fragment) is preferably applied by overlaying the labeled antibody (or fragment) onto a biological sample. Through the use of such a procedure, it is possible to determine not only the presence of the CML progression protein, or conserved variants or peptide fragments, but also its distribution in the examined tissue. Using the present invention, those of ordinary skill will readily perceive that any of a wide variety of histological methods (such as staining procedures) can be modified in order to achieve such in situ detection.

Immunoassays for a CML progression protein or conserved variants or peptide fragments thereof will typically comprise incubating a sample, such as a biological fluid, a tissue extract, freshly harvested cells, or lysates of cells which have been incubated in cell culture, in the presence of a detectably labeled antibody capable of identifying A CML progression protein or conserved variants or peptide fragments thereof, and detecting the bound antibody by any of a number of techniques well-known in the art.

The biological sample may be brought in contact with and immobilized onto a solid phase support or carrier such as nitrocellulose, or other solid support which is capable of immobilizing cells, cell particles or soluble proteins. The support may then be washed with suitable buffers followed by treatment with the detectably labeled antibody specific for a CML progression protein. The solid phase support may then be washed with the buffer a second time to remove unbound antibody. The amount of bound label on solid support may then be detected by conventional means.

By “solid phase support or carrier” is intended any support capable of binding an antigen or an antibody. Well-known supports or carriers include glass, polystyrene, polypropylene, polyethylene, dextran, nylon, amylases, natural and modified celluloses, polyacrylamides, gabbros, and magnetite. The nature of the carrier can be either soluble to some extent or insoluble for the purposes of the present invention. The support material may have virtually any possible structural configuration so long as the coupled molecule is capable of binding to an antigen or antibody. Thus, the support configuration may be spherical, as in a bead, or cylindrical, as in the inside surface of a test tub, or the external surface of a rod. Alternatively, the surface may be flat such as a sheet, test strip, etc. Preferred supports include polystyrene beads. Those skilled in the art will know many other suitable carriers for binding antibody or antigen, or will be able to ascertain the same by use of routine experimentation.

The binding activity of a given lot of an antibody may be determined according to well known methods. Those skilled in the art will be able to determine operative and optimal assay conditions for each determination by employing routine experimentation.

One of the ways in which the antibody specific to a CML progression protein can be detectably labeled is by linking the same to an enzyme and use in an enzyme immunoassay (EIA) (Voller, A., “The Enzyme Linked Immunosorbent Assay (ELISA)”, 1978, Diagnostic Horizons 2:1-7, Microbiological Associates Quarterly Publication, Walkersville, Md.); Voller, A. et al., 1978, J. Clin. Pathol. 31:507-520; Butler, J. E., 1981, Meth. Enzymol. 73:482-523; Maggio, E. (ed.), 1980, Enzyme Immunoassay, CRC Press, Boca Raton, Fla.; Ishikawa, E. et al., (eds.), 1981, Enzyme Immunoassay, Kgaku Shoin, Tokyo). The enzyme which is bound to the antibody will react with an appropriate substrate, preferably a chromogenic substrate, in such a manner as to produce a chemical moiety which can be detected, for example, by spectrophotometric, fluorimetric or by visual means. Enzymes which can be used to detectably label the antibody include, but are not limited to, malate dehydrogenase, staphylococcal nuclease, delta-5-steroid isomerase, yeast alcohol dehydrogenase, alpha-glycerophosphate, dehydrogenase, triose phosphate isomerase, horseradish peroxidase, alkaline phosphatase, asparaginase, glucose oxidase, beta-galactosidase, ribonuclease, urease, catalase, glucose-6-phosphate dehydrogenase, glucoamylase and acetylcholinesterase. The detection can be accomplished by colorimetric methods which employ a chromogenic substrate for the enzyme. Detection may also be accomplished by visual comparison of the extent of enzymatic reaction of a substrate in comparison with similarly prepared standards.

Detection may also be accomplished using any of a variety of other immunoassays. For example, by radioactively labeling the antibodies or antibody fragments, it is possible to detect a CML progression protein through the use of a radioimmunoassay (RIA) (see, for example, Weintraub, B., Principles of Radioimmunoassays, Seventh Training Course on Radioligand Assay Techniques, The Endocrine Society, March, 1986, which is incorporated by reference herein). The radioactive isotope can be detected by such means as the use of a gamma counter or a scintillation counter or by autoradiography.

It is also possible to label the antibody with a fluorescent compound. When the fluorescently labeled antibody is exposed to light of the proper wave length, its presence can then be detected due to fluorescence. Among the most commonly used fluorescent labeling compounds are fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, o-phthaldehyde and fluorescamine.

The antibody can also be detectably labeled using fluorescence emitting metals such as ¹⁵²Eu, or others of the lanthanide series. These metals can be attached to the antibody using such metal chelating groups as diethylenetriaminepentacetic acid (DTPA) or ethylenediaminetetraacetic acid (EDTA).

The antibody also can be detectably labeled by coupling it to a chemiluminescent compound. The presence of the chemiluminescent-tagged antibody is then determined by detecting the presence of luminescence that arises during the course of a chemical reaction. Examples of particularly useful chemiluminescent labeling compounds are luminol, isoluminol, theromatic acridinium ester, imidazole, acridinium salt and oxalate ester.

Likewise, a bioluminescent compound may be used to label the antibody of the present invention. Bioluminescence is a type of chemiluminescence found in biological systems in, which a catalytic protein increases the efficiency of the chemiluminescent reaction. The presence of a bioluminescent protein is determined by detecting the presence of luminescence. Important bioluminescent compounds for purposes of labeling are luciferin, luciferase and aequorin.

An antibody that is specific to a CML progression protein conjugated to detectable substances can be utilized to sort advanced phase CML cells from normal cells by methods known to those of skill in the art. In one embodiment, the advanced phase CML cells are sorted using a fluorescence activated cell sorter (FACS). Fluorescence activated cell sorting (FACS) is a well-known method for separating particles, including cells, based on the fluorescent properties of the particles (Kamarch, 1987, Methods Enzymol, 151:150-165). Laser excitation of fluorescent moieties in the individual particles results in a small electrical charge allowing electromagnetic separation of positive and negative particles from a mixture.

In one embodiment, cells, e.g, cells in bone marrow or peripheral blood, obtained from a patient, e.g., a human, are incubated with fluorescently labeled antibody specific for the CML progression protein for a time sufficient to allow the labeled antibodies to bind to the cells. In an alternative embodiment, such cells are incubated with the antibody, the cells are washed, and the cells are incubated with a second labeled antibody that recognizes the CML progression protein-specific antibody. In accordance with these embodiments, the cells are washed and processed through the cell sorter, allowing separation of cells that bind both antibodies to be separated from hybrid cells that do not bind both antibodies. FACS sorted particles may be directly deposited into individual wells of 96-well or 384-well plates to facilitate separation and further characterization.

5.2.4. Sample Collection

In the present invention, gene products, such as target polynucleotide molecules or proteins, are extracted from a sample taken from a CML patient. The sample may be collected in any clinically acceptable manner, but must be collected such that marker-derived polynucleotides (i.e., RNA) are preserved (if gene expression is to be measured) or proteins are preserved (if encoded proteins are to be measured). In one embodiment, bone marrow samples are used. In another embodiment, peripheral blood samples are used. In one embodiment, the pre-treatment bone marrow or peripheral blood sample from a patient is used. In another embodiment, the treatment bone marrow or peripheral blood sample from a patient after and/or during treatment is used. In one embodiment, the unsorted bone marrow or peripheral blood sample from a patient is used. In one embodiment, the unsorted bone marrow or peripheral blood sample from a clinical chronic phase patient is used. In another embodiment, the sorted bone marrow or peripheral blood sample from a patient after and/or during treatment is used. Other suitable samples may comprise any clinically relevant tissue sample, such as a tumor biopsy or fine needle aspirate, or a sample of body fluid, such as blood, plasma, serum, lymph, ascitic fluid, cystic fluid, or urine. The sample may be taken from a human, or, in a veterinary context, from non-human animals such as ruminants, horses, swine or sheep, or from domestic companion animals such as felines and canines.

In a specific embodiment, mRNA or nucleic acids derived therefrom (i.e., cDNA or amplified RNA or amplified DNA) are preferably labeled distinguishably from polynucleotide molecules of a reference sample, and both are simultaneously or independently hybridized to a microarray comprising some or all of the markers or marker sets or subsets described above. Alternatively, mRNA or nucleic acids derived therefrom may be labeled with the same label as the reference polynucleotide molecules, wherein the intensity of hybridization of each at a particular probe is compared.

Methods for preparing total and poly(A)+ RNA are well known and are described generally in Sambrook et al., MOLECULAR CLONING—A LABORATORY MANUAL (2ND ED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989)) and Ausubel et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, vol. 2, Current Protocols Publishing, New York (1994)). Preferably, total RNA, or total mRNA (poly(A)+ RNA) is measured in the methods of the invention directly or indirectly (e.g., via measuring cDNA or cRNA).

RNA may be isolated from eukaryotic cells by procedures that involve lysis of the cells and denaturation of the proteins contained therein. Cells of interest include wild-type cells (i.e., non-cancerous), drug-exposed wild-type cells, tumor- or tumor-derived cells, modified cells, normal or tumor cell line cells, and drug-exposed modified cells. Preferably, the cells are breast cancer tumor cells.

Additional steps may be employed to remove DNA. Cell lysis may be accomplished with a nonionic detergent, followed by microcentrifugation to remove the nuclei and hence the bulk of the cellular DNA. In one embodiment, RNA is extracted from cells of the various types of interest using guanidinium thiocyanate lysis followed by CsCl centrifugation to separate the RNA from DNA (Chirgwin et al., Biochemistry 18:5294-5299 (1979)). Poly(A)+ RNA is selected by selection with oligo-dT cellulose (see Sambrook et al., MOLECULAR CLONING—A LABORATORY MANUAL (2ND ED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989). Alternatively, separation of RNA from DNA can be accomplished by organic extraction, for example, with hot phenol or phenol/chloroform/isoamyl alcohol.

If desired, RNase inhibitors may be added to the lysis buffer. Likewise, for certain cell types, it may be desirable to add a protein denaturation/digestion step to the protocol.

For many applications, it is desirable to preferentially enrich mRNA with respect to other cellular RNAs, such as transfer RNA (tRNA) and ribosomal RNA (rRNA). Most mRNAs contain a poly(A) tail at their 3′ end. This allows them to be enriched by affinity chromatography, for example, using oligo(dT) or poly(U) coupled to a solid support, such as cellulose or Sephadex™ (see Ausubel et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, vol. 2, Current Protocols Publishing, New York (1994). Once bound, poly(A)+ mRNA is eluted from the affinity column using 2 mM EDTA/0.1% SDS.

In a specific embodiment, total RNA or total mRNA from cells is used in the methods of the invention. The source of the RNA can be cells of an animal, e.g., human, mammal, primate, non-human animal, dog, cat, mouse, rat, bird, etc. In specific embodiments, the method of the invention is used with a sample containing total mRNA or total RNA from 1×10⁶ cells or less. In another embodiment, proteins can be isolated from the foregoing sources, by methods known in the art, for use in expression analysis at the protein level.

Probes to the homologs of the marker sequences disclosed herein can be employed preferably when non-human nucleic acid is being assayed.

5.2.5. Determination of Abundance Levels of Gene Products

The abundance levels of the gene products of the genes in a sample may be determined by any means known in the art. The levels may be determined by isolating and determining the level (i.e., amount) of nucleic acid transcribed from each marker gene. Alternatively, or additionally, the level of specific proteins encoded by a marker gene may be determined.

The levels of transcripts of specific marker genes can be accomplished by determining the amount of mRNA, or polynucleotides derived therefrom, present in a sample. Any method for determining RNA levels can be used. For example, RNA is isolated from a sample and separated on an agarose gel. The separated RNA is then transferred to a solid support, such as a filter. Nucleic acid probes representing one or more markers are then hybridized to the filter by northern hybridization, and the amount of marker-derived RNA is determined. Such determination can be visual, or machine-aided, for example, by use of a densitometer. Another method of determining RNA levels is by use of a dot-blot or a slot-blot. In this method, RNA, or nucleic acid derived therefrom, from a sample is labeled. The RNA or nucleic acid derived therefrom is then hybridized to a filter containing oligonucleotides derived from one or more marker genes, wherein the oligonucleotides are placed upon the filter at discrete, easily-identifiable locations. Hybridization, or lack thereof, of the labeled RNA to the filter-bound oligonucleotides is determined visually or by densitometer. Polynucleotides can be labeled using a radiolabel or a fluorescent (i.e., visible) label.

The levels of transcripts of particular marker genes may also be assessed by determining the level of the specific protein expressed from the marker genes. This can be accomplished, for example, by separation of proteins from a sample on a polyacrylamide gel, followed by identification of specific marker-derived proteins using antibodies in a western blot. Alternatively, proteins can be separated by two-dimensional gel electrophoresis systems. Two-dimensional gel electrophoresis is well-known in the art and typically involves isoelectric focusing along a first dimension followed by SDS-PAGE electrophoresis along a second dimension. See, e.g., Hames et al, 1990, GEL ELECTROPHORESIS OF PROTEINS: A PRACTICAL APPROACH, IRL Press, New York; Shevchenko et al., Proc. Nat'l Acad. Sci. USA 93:1440-1445 (1996); Sagliocco et al., Yeast 12:1519-1533 (1996); Lander, Science 274:536-539 (1996). The resulting electropherograms can be analyzed by numerous techniques, including mass spectrometric techniques, western blotting and immunoblot analysis using polyclonal and monoclonal antibodies.

Alternatively, marker-derived protein levels can be determined by constructing an antibody microarray in which binding sites comprise immobilized, preferably monoclonal, antibodies specific to a plurality of protein species encoded by the cell genome. Preferably, antibodies are present for a substantial fraction of the marker-derived proteins of interest. Methods for making monoclonal antibodies are well known (see, e.g., Harlow and Lane, 1988, ANTIBODIES: A LABORATORY MANUAL, Cold Spring Harbor, N.Y., which is incorporated in its entirety for all purposes). In one embodiment, monoclonal antibodies are raised against synthetic peptide fragments designed based on genomic sequence of the cell. With such an antibody array, proteins from the cell are contacted to the array, and their binding is assayed with assays known in the art. Generally, the expression, and the level of expression, of proteins of diagnostic or prognostic interest can be detected through immunohistochemical staining of tissue slices or sections.

Finally, levels of transcripts of marker genes in a number of tissue specimens may be characterized using a “tissue array” (Kononen et al., Nat. Med 4(7):844-7 (1998)). In a tissue array, multiple tissue samples are assessed on the same microarray. The arrays allow in situ detection of RNA and protein levels; consecutive sections allow the analysis of multiple samples simultaneously.

5.2.5.1. Microarrays

In preferred embodiments, polynucleotide microarrays are used to measure expression so that the expression status of each of the markers above is assessed simultaneously. Generally, microarrays according to the invention comprise a plurality of markers informative for clinical category determination, for a particular disease or condition.

The invention also provides a microarray comprising for each of a plurality of genes, said genes being all or at least 5, 10, 20, 30, 40, 50, 70, 100 or 200 of the genes listed in Tables 1a and/or 1b or any of Tables 2a-2b, 4 and 5a-5b, or all or at least 5, 10, or 15 of the genes listed in Table 3, one or more polynucleotide probes complementary and hybridizable to a sequence in said gene, wherein polynucleotide probes complementary and hybridizable to said genes constitute at least 50%, 60%, 70%, 80%, 90%, 95%, or 98% of the probes on said microarray. In a particular embodiment, the invention provides such a microarray wherein the plurality of genes comprises the 20 genes listed in Table 3 or the 228 genes listed in Table 4 or the 368 genes listed in Tables 5a and 5b. The microarray can be in a sealed container.

The microarrays preferably comprise at least 2, 3, 4, 5, 7, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, 100, 150, 200 or more of markers, or all of the markers, or any combination of markers, identified as informative for CML progression and/or imatinib resistance, e.g., within Tables 1a and 1b or any of Tables 2a-2b, 3, 4, and 5a-5b. The actual number of informative markers the microarray comprises will vary depending upon the particular condition of interest.

In other embodiments, the invention provides polynucleotide arrays in which the CML progression markers comprise at least 50%, 60%, 70%, 80%, 85%, 90%, 95% or 98% of the probes on the array. In another specific embodiment, the microarray comprises a plurality of probes, wherein said plurality of probes comprise probes complementary and hybridizable to at least 75% of the CML progression markers.

General methods pertaining to the construction of microarrays comprising the marker sets and/or subsets above are described in the following sections.

5.2.5.2. Construction of Microarrays

Microarrays are prepared by selecting probes which comprise a polynucleotide sequence, and then immobilizing such probes to a solid support or surface. For example, the probes may comprise DNA sequences, RNA sequences, or copolymer sequences of DNA and RNA. The polynucleotide sequences of the probes may also comprise DNA and/or RNA analogues, or combinations thereof. For example, the polynucleotide sequences of the probes may be full or partial fragments of genomic DNA. The polynucleotide sequences of the probes may also be synthesized nucleotide sequences, such as synthetic oligonucleotide sequences. The probe sequences can be synthesized either enzymatically in vivo, enzymatically in vitro (e.g., by PCR), or non-enzymatically in vitro.

The probe or probes used in the methods of the invention are preferably immobilized to a solid support which may be either porous or non-porous. For example, the probes may be polynucleotide sequences which are attached to a nitrocellulose or nylon membrane or filter covalently at either the 3′ or the 5′ end of the polynucleotide. Such hybridization probes are well known in the art (see, e.g., Sambrook et al., MOLECULAR CLONING—A LABORATORY MANUAL (2ND ED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989). Alternatively, the solid support or surface may be a glass or plastic surface. In a particularly preferred embodiment, hybridization levels are measured to microarrays of probes consisting of a solid phase on the surface of which are immobilized a population of polynucleotides, such as a population of DNA or DNA mimics, or, alternatively, a population of RNA or RNA mimics. The solid phase may be a nonporous or, optionally, a porous material such as a gel.

In preferred embodiments, a microarray comprises a support or surface with an ordered array of binding (e.g., hybridization) sites or “probes” each representing one of the markers described herein. Preferably the microarrays are addressable arrays, and more preferably positionally addressable arrays. More specifically, each probe of the array is preferably located at a known, predetermined position on the solid support such that the identity (i.e., the sequence) of each probe can be determined from its position in the array (i.e., on the support or surface). In preferred embodiments, each probe is covalently attached to the solid support at a single site.

Microarrays can be made in a number of ways, of which several are described below. However produced, microarrays share certain characteristics. The arrays are reproducible, allowing multiple copies of a given array to be produced and easily compared with each other. Preferably, microarrays are made from materials that are stable under binding (e.g., nucleic acid hybridization) conditions. The microarrays are preferably small, e.g., between 1 cm² and 25 cm², between 12 cm² and 13 cm², or 3 cm². However, larger arrays are also contemplated and may be preferable, e.g., for use in screening arrays. Preferably, a given binding site or unique set of binding sites in the microarray will specifically bind (e.g., hybridize) to the product of a single gene in a cell (e.g., to a specific mRNA, or to a specific cDNA derived therefrom). However, in general, other related or similar sequences will cross hybridize to a given binding site.

The microarrays of the present invention include one or more test probes, each of which has a polynucleotide sequence that is complementary to a subsequence of RNA or DNA to be detected. Preferably, the position of each probe on the solid surface is known. Indeed, the microarrays are preferably positionally addressable arrays. Specifically, each probe of the array is preferably located at a known, predetermined position on the solid support such that the identity (i.e., the sequence) of each probe can be determined from its position on the array (i.e., on the support or surface).

According to the invention, the microarray is an array (i.e., a matrix) in which each position represents one of the markers described herein. For example, each position can contain a DNA or DNA analogue based on genomic DNA to which a particular RNA or cDNA transcribed from that genetic marker can specifically hybridize. The DNA or DNA analogue can be, e.g., a synthetic oligomer or a gene fragment. In one embodiment, probes representing each of the markers are present on the array. In a preferred embodiment, the array comprises probes for each of the markers listed in Tables 1a and/or 1b or any one of Tables 2a-2b, 3, 4, and 5a-5b.

5.2.5.3. Preparing Probes for Microarrays

As noted above, the “probe” to which a particular polynucleotide molecule specifically hybridizes according to the invention contains a complementary genomic polynucleotide sequence. The probes of the microarray preferably consist of nucleotide sequences of no more than 1,000 nucleotides. In some embodiments, the probes of the array consist of nucleotide sequences of 10 to 1,000 nucleotides. In a preferred embodiment, the nucleotide sequences of the probes are in the range of 10-200 nucleotides in length and are genomic sequences of a species of organism, such that a plurality of different probes is present, with sequences complementary and thus capable of hybridizing to the genome of such a species of organism, sequentially tiled across all or a portion of such genome. In other specific embodiments, the probes are in the range of 10-30 nucleotides in length, in the range of 10-40 nucleotides in length, in the range of 20-50 nucleotides in length, in the range of 40-80 nucleotides in length, in the range of 50-150 nucleotides in length, in the range of 80-120 nucleotides in length, and most preferably are 60 nucleotides in length.

The probes may comprise DNA or DNA “mimics” (e.g., derivatives and analogues) corresponding to a portion of an organism's genome. In another embodiment, the probes of the microarray are complementary RNA or RNA mimics. DNA mimics are polymers composed of subunits capable of specific, Watson-Crick-like hybridization with DNA, or of specific hybridization with RNA. The nucleic acids can be modified at the base moiety, at the sugar moiety, or at the phosphate backbone. Exemplary DNA mimics include, e.g., phosphorothioates.

DNA can be obtained, e.g., by polymerase chain reaction (PCR) amplification of genomic DNA or cloned sequences. PCR primers are preferably chosen based on a known sequence of the genome that will result in amplification of specific fragments of genomic DNA. Computer programs that are well known in the art are useful in the design of primers with the required specificity and optimal amplification properties, such as Oligo version 5.0 (National Biosciences). Typically each probe on the microarray will be between 10 bases and 50,000 bases, usually between 300 bases and 1,000 bases in length. PCR methods are well known in the art, and are described, for example, in Innis et al., eds., PCR PROTOCOLS: A GUIDE TO METHODS AND APPLICATIONS, Academic Press Inc., San Diego, Calif. (1990). It will be apparent to one skilled in the art that controlled robotic systems are useful for isolating and amplifying nucleic acids.

An alternative, preferred means for generating the polynucleotide probes of the microarray is by synthesis of synthetic polynucleotides or oligonucleotides, e.g., using N-phosphonate or phosphoramidite chemistries (Froehler et al., Nucleic Acid Res. 14:5399-5407 (1986); McBride et al., Tetrahedron Lett. 24:246-248 (1983)). Synthetic sequences are typically between about 10 and about 500 bases in length, more typically between about 20 and about 100 bases, and most preferably between about 40 and about 70 bases in length. In some embodiments, synthetic nucleic acids include non-natural bases, such as, but by no means limited to, inosine. As noted above, nucleic acid analogues may be used as binding sites for hybridization. An example of a suitable nucleic acid analogue is peptide nucleic acid (see, e.g., Egholm et al., Nature 363:566-568 (1993); U.S. Pat. No. 5,539,083).

Probes are preferably selected using an algorithm that takes into account binding energies, base composition, sequence complexity, cross-hybridization binding energies, and secondary structure. See Friend et al., International Patent Publication WO 01/05935, published Jan. 25, 2001; Hughes et al., Nat. Biotech. 19:342-7 (2001).

A skilled artisan will also appreciate that positive control probes, e.g., probes known to be complementary and hybridizable to sequences in the target polynucleotide molecules, and negative control probes, e.g., probes known to not be complementary and hybridizable to sequences in the target polynucleotide molecules, should be included on the array. In one embodiment, positive controls are synthesized along the perimeter of the array. In another embodiment, positive controls are synthesized in diagonal stripes across the array. In still another embodiment, the reverse complement for each probe is synthesized next to the position of the probe to serve as a negative control. In yet another embodiment, sequences from other species of organism are used as negative controls or as “spike-in” controls.

5.2.5.4. Attaching Probes to the Solid Surface

The probes are attached to a solid support or surface, which may be made, e.g., from glass, plastic (e.g., polypropylene, nylon), polyacrylamide, nitrocellulose, gel, or other porous or nonporous material. A preferred method for attaching the nucleic acids to a surface is by printing on glass plates, as is described generally by Schena et al, Science 270:467-470 (1995). This method is especially useful for preparing microarrays of cDNA (See also, DeRisi et al, Nature Genetics 14:457-460 (1996); Shalon et al., Genome Res. 6:639-645 (1996); and Schena et al., Proc. Natl. Acad. Sci. U.S.A. 93:10539-11286 (1995)).

A second preferred method for making microarrays is by making high-density oligonucleotide arrays. Techniques are known for producing arrays containing thousands of oligonucleotides complementary to defined sequences, at defined locations on a surface using photolithographic techniques for synthesis in situ (see, Fodor et al., 1991, Science 251:767-773; Pease et al., 1994, Proc. Natl. Acad. Sci. U.S.A. 91:5022-5026; Lockhart et al., 1996, Nature Biotechnology 14:1675; U.S. Pat. Nos. 5,578,832; 5,556,752; and 5,510,270) or other methods for rapid synthesis and deposition of defined oligonucleotides (Blanchard et al., Biosensors & Bioelectronics 11:687-690). When these methods are used, oligonucleotides (e.g., 60-mers) of known sequence are synthesized directly on a surface such as a derivatized glass slide. Usually, the array produced is redundant, with several oligonucleotide molecules per RNA.

Other methods for making microarrays, e.g., by masking (Maskos and Southern, 1992, Nuc. Acids. Res. 20:1679-1684), may also be used. In principle, and as noted supra, any type of array, for example, dot blots on a nylon hybridization membrane (see Sambrook et al., MOLECULAR CLONING—A LABORATORY MANUAL (2ND ED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989)) could be used. However, as will be recognized by those skilled in the art, very small arrays will frequently be preferred because hybridization volumes will be smaller.

In one embodiment, the arrays of the present invention are prepared by synthesizing polynucleotide probes on a support. In such an embodiment, polynucleotide probes are attached to the support covalently at either the 3′ or the 5′ end of the polynucleotide.

In a particularly preferred embodiment, microarrays are manufactured by means of an ink jet printing device for oligonucleotide synthesis, e.g., using the methods and systems described by Blanchard in U.S. Pat. No. 6,028,189; Blanchard et al., 1996, Biosensors and Bioelectronics 11:687-690; Blanchard, 1998, in Synthetic DNA Arrays in Genetic Engineering, Vol. 20, J. K. Setlow, Ed., Plenum Press, New York at pages 111-123. Specifically, the oligonucleotide probes in such microarrays are preferably synthesized in arrays, e.g., on a glass slide, by serially depositing individual nucleotide bases in “microdroplets” of a high surface tension solvent such as propylene carbonate. The microdroplets have small volumes (e.g., 100 pL or less, more preferably 50 pL or less) and are separated from each other on the microarray (e.g., by hydrophobic domains) to form circular surface tension wells which define the locations of the array elements (i.e., the different probes). Microarrays manufactured by this ink-jet method are typically of high density, preferably having a density of at least about 2,500 different probes per 1 cm². The polynucleotide probes are attached to the support covalently at either the 3′ or the 5′ end of the polynucleotide.

5.2.5.5. Target Labeling and Hybridization to Microarrays

The polynucleotide molecules which may be analyzed by the present invention (the “target polynucleotide molecules”) may be from any clinically relevant source, but are expressed RNA or a nucleic acid derived therefrom (e.g., cDNA or amplified RNA derived from cDNA that incorporates an RNA polymerase promoter), including naturally occurring nucleic acid molecules, as well as synthetic nucleic acid molecules. In one embodiment, the target polynucleotide molecules comprise RNA, including, but by no means limited to, total cellular RNA, poly(A)⁺ messenger RNA (mRNA) or fraction thereof, cytoplasmic mRNA, or RNA transcribed from cDNA (i.e., cRNA; see, e.g., Linsley & Schelter, U.S. patent application Ser. No. 09/411,074, filed Oct. 4, 1999, or U.S. Pat. No. 5,545,522, 5,891,636, or 5,716,785). Methods for preparing total and poly(A)⁺ RNA are well known in the art, and are described generally, e.g., in Sambrook et al., MOLECULAR CLONING—A LABORATORY MANUAL (2ND ED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989). In one embodiment, RNA is extracted from cells of the various types of interest in this invention using guanidinium thiocyanate lysis followed by CsCl centrifugation (Chirgwin et al., 1979, Biochemistry 18:5294-5299). In another embodiment, total RNA is extracted using a silica gel-based column, commercially available examples of which include RNeasy (Qiagen, Valencia, Calif.) and StrataPrep (Stratagene, La Jolla, Calif.). In an alternative embodiment, which is preferred for S. cerevisiae, RNA is extracted from cells using phenol and chloroform, as described in Ausubel et al., eds., 1989, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, Vol. III, Green Publishing Associates, Inc., John Wiley & Sons, Inc., New York, at pp. 13.12.1-13.12.5). Poly(A)⁺ RNA can be selected, e.g., by selection with oligo-dT cellulose or, alternatively, by oligo-dT primed reverse transcription of total cellular RNA. In one embodiment, RNA can be fragmented by methods known in the art, e.g., by incubation with ZnCl₂, to generate fragments of RNA. In another embodiment, the polynucleotide molecules analyzed by the invention comprise cDNA, or PCR products of amplified RNA or cDNA.

In one embodiment, total RNA, mRNA, or nucleic acids derived therefrom, is isolated from a sample taken from a CML patient. Target polynucleotide molecules that are poorly expressed in particular cells may be enriched using normalization techniques (Bonaldo et al., 1996, Genome Res. 6:791-806).

As described above, the target polynucleotides are detectably labeled at one or more nucleotides. Any method known in the art may be used to detectably label the target polynucleotides. Preferably, this labeling incorporates the label uniformly along the length of the RNA, and more preferably, the labeling is carried out at a high degree of efficiency. One embodiment for this labeling uses oligo-dT primed reverse transcription to incorporate the label; however, conventional methods of this method are biased toward generating 3′ end fragments. Thus, in a preferred embodiment, random primers (e.g., 9-mers) are used in reverse transcription to uniformly incorporate labeled nucleotides over the full length of the target polynucleotides. Alternatively, random primers may be used in conjunction with PCR methods or T7 promoter-based in vitro transcription methods in order to amplify the target polynucleotides.

In a preferred embodiment, the detectable label is a luminescent label. For example, fluorescent labels, bioluminescent labels, chemiluminescent labels, and colorimetric labels may be used in the present invention. In a highly preferred embodiment, the label is a fluorescent label, such as a fluorescein, a phosphor, a rhodamine, or a polymethine dye derivative. Examples of commercially available fluorescent labels include, for example, fluorescent phosphoramidites such as FluorePrime (Amersham Pharmacia, Piscataway, N.J.), Fluoredite (Miilipore, Bedford, Mass.), FAM (ABI, Foster City, Calif.), and Cy3 or Cy5 (Amersham Pharmacia, Piscataway, N.J.). In another embodiment, the detectable label is a radiolabeled nucleotide.

In a further preferred embodiment, target polynucleotide molecules from a patient sample are labeled differentially from target polynucleotide molecules of a reference sample. The reference can comprise target polynucleotide molecules from normal cell samples (i.e., cell sample, e.g., bone marrow or peripheral blood, from those not afflicted with CML) or from cell samples, e.g., bone marrow or peripheral blood, from chronic phase CML patients.

Nucleic acid hybridization and wash conditions are chosen so that the target polynucleotide molecules specifically bind or specifically hybridize to the complementary polynucleotide sequences of the array, preferably to a specific array site, wherein its complementary DNA is located.

Arrays containing double-stranded probe DNA situated thereon are preferably subjected to denaturing conditions to render the DNA single-stranded prior to contacting with the target polynucleotide molecules. Arrays containing single-stranded probe DNA (e.g., synthetic oligodeoxyribonucleic acids) may need to be denatured prior to contacting with the target polynucleotide molecules, e.g., to remove hairpins or dimers which form due to self complementary sequences.

Optimal hybridization conditions will depend on the length (e.g., oligomer versus polynucleotide greater than 200 bases) and type (e.g., RNA, or DNA) of probe and target nucleic acids. One of skill in the art will appreciate that as the oligonucleotides become shorter, it may become necessary to adjust their length to achieve a relatively uniform melting temperature for satisfactory hybridization results. General parameters for specific (i.e., stringent) hybridization conditions for nucleic acids are described in Sambrook et al., MOLECULAR CLONING—A LABORATORY MANUAL (2ND ED.), Vols. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989), and in Ausubel et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, vol. 2, Current Protocols Publishing, New York (1994). Typical hybridization conditions for the cDNA microarrays of Schena et al. are hybridization in 5×SSC plus 0.2% SDS at 65° C. for four hours, followed by washes at 25° C. in low stringency wash buffer (1×SSC plus 0.2% SDS), followed by 10 minutes at 25° C. in higher stringency wash buffer (0.1×SSC plus 0.2% SDS) (Schena et al., Proc. Natl. Acad. Sci. U.S.A. 93:10614 (1993)). Useful hybridization conditions are aiso provided in, e.g., Tijessen, 1993, HYBRIDIZATION WITH NUCLEIC ACID PROBES, Elsevier Science Publishers B.V.; and Kricka, 1992, NONISOTOPIC DNA PROBE TECHNIQUES, Academic Press, San Diego, Calif.

Particularly preferred hybridization conditions include hybridization at a temperature at or near the mean melting temperature of the probes (e.g., within 51° C., more preferably within 21° C.) in 1 M NaCl, 50 mM MES buffer (pH 6.5), 0.5% sodium sarcosine and 30% formamide.

5.2.5.6. Signal Detection and Data Analysis

When fluorescently labeled gene products are used, the fluorescence emissions at each site of a microarray may be, preferably, detected by scanning confocal laser microscopy. In one embodiment, a separate scan, using the appropriate excitation line, is carried out for each of the two fluorophores used. Alternatively, a laser may be used that allows simultaneous specimen illumination at wavelengths specific to the two fluorophores and emissions from the two fluorophores can be analyzed simultaneously (see Shalon et al., 1996, “A DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization,” Genome Research 6:639-645, which is incorporated by reference in its entirety for all purposes). In a preferred embodiment, the arrays are scanned with a laser fluorescent scanner with a computer controlled X-Y stage and a microscope objective. Sequential excitation of the two fluorophores is achieved with a multi-line, mixed gas laser and the emitted light is split by wavelength and detected with two photomultiplier tubes. Fluorescence laser scanning devices are described in Schena et al., Genome Res. 6:639-645 (1996), and in other references cited herein. Alternatively, the fiber-optic bundle described by Ferguson et al., Nature Biotech. 14:1681-1684 (1996), may be used to monitor mRNA abundance levels at a large number of sites simultaneously.

5.2.5.7. Other Assays for Detecting and Quantifying RNA

In addition to microarrays such as those described above any technique known to one of skill for detecting and measuring RNA can be used in accordance with the methods of the invention. Non-limiting examples of techniques include Northern blotting, nuclease protection assays, RNA fingerprinting, polymerase chain reaction, ligase chain reaction, Qbeta replicase, isothermal amplification method, strand displacement amplification, transcription based amplification systems, nuclease protection (S1 nuclease or RNAse protection assays), SAGE as well as methods disclosed in International Publication Nos. WO 88/10315 and WO 89/06700, and International Applications Nos. PCT/US87/00880 and PCT/US89/01025.

A standard Northern blot assay can be used to ascertain an RNA transcript size, identify alternatively spliced RNA transcripts, and the relative amounts of mRNA in a sample, in accordance with conventional Northern hybridization techniques known to those persons of ordinary skill in the art. In Northern blots, RNA samples are first separated by size via electrophoresis in an agarose gel under denaturing conditions. The RNA is then transferred to a membrane, crosslinked and hybridized with a labeled probe. Nonisotopic or high specific activity radiolabeled probes can be used including random-primed, nick-translated, or PCR-generated DNA probes, in vitro transcribed RNA probes, and oligonucleotides. Additionally, sequences with only partial homology (e.g., cDNA from a different species or genomic DNA fragments that might contain an exon) may be used as probes. The labeled probe, e.g., a radiolabelled cDNA, either containing the full-length, single stranded DNA or a fragment of that DNA sequence may be at least 20, at least 30, at least 50, or at least 100 consecutive nucleotides in length. The probe can be labeled by any of the many different methods known to those skilled in this art. The labels most commonly employed for these studies are radioactive elements, enzymes, chemicals that fluoresce when exposed to ultraviolet light, and others. A number of fluorescent materials are known and can be utilized as labels. These include, but are not limited to, fluorescein, rhodamine, auramine, Texas Red, AMCA blue and Lucifer Yellow. A particular detecting material is anti-rabbit antibody prepared in goats and conjugated with fluorescein through an isothiocyanate. Proteins can also be labeled with a radioactive element or with an enzyme. The radioactive label can be detected by any of the currently available counting procedures. Non-limiting examples of isotopes include ³H, ¹⁴C, ³²P, ³⁵S, ³⁶Cl, ³⁵Cr, ⁵⁷Co, ⁵⁸Co, ⁵⁹Fe, ⁹⁰Y, ¹²⁵I, ¹³¹I, and ¹⁸⁶Re. Enzyme labels are likewise useful, and can be detected by any of the presently utilized colorimetric, spectrophotometric, fluorospectrophotometric, amperometric or gasometric techniques. The enzyme is conjugated to the selected particle by reaction with bridging molecules such as carbodiimides, diisocyanates, glutaraldehyde and the like. Any enzymes known to one of skill in the art can be utilized. Examples of such enzymes include, but are not limited to, peroxidase, beta-D-galactosidase, urease, glucose oxidase plus peroxidase and alkaline phosphatase. U.S. Pat. Nos. 3,654,090, 3,850,752, and 4,016,043 are referred to by way of example for their disclosure of alternate labeling material and methods.

Nuclease protection assays (including both ribonuclease protection assays and S1 nuclease assays) can be used to detect and quantitate specific mRNAs. In nuclease protection assays, an antisense probe (labeled with, e.g., radiolabeled or nonisotopic) hybridizes in solution to an RNA sample. Following hybridization, single-stranded, unhybridized probe and RNA are degraded by nucleases. An acrylamide gel is used to separate the remaining protected fragments. Typically, solution hybridization is more efficient than membrane-based hybridization, and it can accommodate up to 100 μg of sample RNA, compared with the 20-30 μg maximum of blot hybridizations.

The ribonuclease protection assay, which is the most common type of nuclease protection assay, requires the use of RNA probes. Oligonucleotides and other single-stranded DNA probes can only be used in assays containing S1 nuclease. The single-stranded, antisense probe must typically be completely homologous to target RNA to prevent cleavage of the probe:target hybrid by nuclease.

Serial Analysis Gene Expression (SAGE), which is described in e.g., Velculescu et al., 1995, Science 270:484-7; Carulli, et al., 1998, Journal of Cellular Biochemistry Supplements 30/31:286-96, can also be used to determine RNA abundances in a cell sample.

Quantitative reverse transcriptase PCR (qRT-PCR) can also be used to determine the expression profiles of marker genes (see, e.g., U.S. Patent Application Publication No. 2005/0048542A1). The first step in gene expression profiling by RT-PCR is the reverse transcription of the RNA template into cDNA, followed by its exponential amplification in a PCR reaction. The two most commonly used reverse transcriptases are avilo myeloblastosis virus reverse transcriptase (AMV-RT) and Moloney murine leukemia virus reverse transcriptase (MLV-RT). The reverse transcription step is typically primed using specific primers, random hexamers, or oligo-dT primers, depending on the circumstances and the goal of expression profiling. For example, extracted RNA can be reverse-transcribed using a GeneAmp RNA PCR kit (Perkin Elmer, Calif., USA), following the manufacturer's instructions. The derived cDNA can then be used as a template in the subsequent PCR reaction.

Although the PCR step can use a variety of thermostable DNA-dependent DNA polymerases, it typically employs the Taq DNA polymerase, which has a 5′-3′ nuclease activity but lacks a 3′-5′ proofreading endonuclease activity. Thus, TaqMan® PCR typically utilizes the 5′-nuclease activity of Taq or Tth polymerase to hydrolyze a hybridization probe bound to its target amplicon, but any enzyme with equivalent 5′ nuclease activity can be used. Two oligonucleotide primers are used to generate an amplicon typical of a PCR reaction. A third oligonucleotide, or probe, is designed to detect nucleotide sequence located between the two PCR primers. The probe is non-extendible by Taq DNA polymerase enzyme, and is labeled with a reporter fluorescent dye and a quencher fluorescent dye. Any laser-induced emission from the reporter dye is quenched by the quenching dye when the two dyes are located close together as they are on the probe. During the amplification reaction, the Taq DNA polymerase enzyme cleaves the probe in a template-dependent manner. The resultant probe fragments disassociate in solution, and signal from the released reporter dye is free from the quenching effect of the second fluorophore. One molecule of reporter dye is liberated for each new molecule synthesized, and detection of the unquenched reporter dye provides the basis for quantitative interpretation of the data.

TaqMan® RT-PCR can be performed using commercially available equipment, such as, for example, ABI PRISM 7700™. Sequence Detection System™ (Perkin-Elmer-Applied Biosystems, Foster City, Calif., USA), or Lightcycler (Roche Molecular Biochemicals, Mannheim, Germany). In a preferred embodiment, the 5′ nuclease procedure is run on a real-time quantitative PCR device such as the ABI PRISM 7700™ Sequence Detection System™. The system consists of a thermocycler, laser, charge-coupled device (CCD), camera and computer. The system includes software for running the instrument and for analyzing the data.

5′-Nuclease assay data are initially expressed as Ct, or the threshold cycle. Fluorescence values are recorded during every cycle and represent the amount of product amplified to that point in the amplification reaction. The point when the fluorescent signal is first recorded as statistically significant is the threshold cycle (Ct).

To minimize errors and the effect of sample-to-sample variation, RT-PCR is usually performed using an internal standard. The ideal internal standard is expressed at a constant level among different tissues, and is unaffected by the experimental treatment. RNAs most frequently used to normalize patterns of gene expression are mRNAs for the housekeeping genes glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) and β-actin.

A more recent variation of the RT-PCR technique is the real time quantitative PCR, which measures PCR product accumulation through a dual-labeled fluorigenic probe (i.e., TaqMan® probe). Real time PCR is compatible both with quantitative competitive PCR, where internal competitor for each target sequence is used for normalization, and with quantitative comparative PCR using a normalization gene contained within the sample, or a housekeeping gene for RT-PCR. For further details see, e.g. Held et al., Genome Research 6:986-994 (1996).

5.2.5.8. Detection and Quantification of Protein

Measurement of the translational state may be performed according to several methods. For example, whole genome monitoring of protein (e.g., the “proteome,”) can be carried out by constructing a microarray in which binding sites comprise immobilized, preferably monoclonal, antibodies specific to a plurality of protein species encoded by the cell genome. Preferably, antibodies are present for a substantial fraction of the encoded proteins, or at least for those proteins relevant to the action of a drug of interest. Methods for making monoclonal antibodies are well known (see, e.g., Harlow and Lane, 1988, Antibodies: A Laboratory Manual, Cold Spring Harbor, N.Y., which is incorporated in its entirety for all purposes). In one embodiment, monoclonal antibodies are raised against synthetic peptide fragments designed based on genomic sequence of the cell. With such an antibody array, proteins from the cell are contacted to the array and their binding is assayed with assays known in the art.

Immunoassays known to one of skill in the art can be used to detect and quantify protein levels. For example, ELISAs can be used to detect and quantify protein levels. ELISAs comprise preparing antigen, coating the well of a 96 well microtiter plate with the antigen, adding the antibody of interest conjugated to a detectable compound such as an enzymatic substrate (e.g., horseradish peroxidase or alkaline phosphatase) to the well and incubating for a period of time, and detecting the presence of the antigen. In ELISAs the antibody of interest does not have to be conjugated to a detectable compound; instead, a second antibody (which recognizes the antibody of interest) conjugated to a detectable compound may be added to the well. Further, instead of coating the well with the antigen, the antibody may be coated to the well. In this case, a second antibody conjugated to a detectable compound may be added following the addition of the antigen of interest to the coated well. One of skill in the art would be knowledgeable as to the parameters that can be modified to increase the signal detected as well as other variations of ELISAs known in the art. In a preferred embodiment, an ELISA may be performed by coating a high binding 96-well microtiter plate (Costar) with 2 μg/ml of rhu-IL-9 in PBS overnight. Following three washes with PBS, the plate is incubated with three-fold serial dilutions of Fab at 25° C. for 1 hour. Following another three washes of PBS, 1 μg/ml anti-human kappa-alkaline phosphatase-conjugate is added and the plate is incubated for 1 hour at 25° C. Following three washes with PBST, the alkaline phosphatase activity is determined in 50 μl/AMP/PPMP substrate. The reactions are stopped and the absorbance at 560 nm is determined with a VMAX microplate reader. For further discussion regarding ELISAs see, e.g., Ausubel et al, eds, 1994, Current Protocols in Molecular Biology, Vol. 1, John Wiley & Sons, Inc., New York at 11.2.1.

Protein levels may be determined by Western blot analysis. Further, protein levels as well as the phosphorylation of proteins can be determined by immunoprecitation followed by Western blot analysis. Immunoprecipitation protocols generally comprise lysing a population of cells in a lysis buffer such as RIPA buffer (1% NP-40 or Triton X-100, 1% sodium deoxycholate, 0.1% SDS, 0.15 M NaCl, 0.01 M sodium phosphate at pH 7.2, 1% Trasylol) supplemented with protein phosphatase and/or protease inhibitors (e.g., EDTA, PMSF, aprotinin, sodium vanadate), adding the antibody of interest to the cell lysate, incubating for a period of time (e.g., 1 to 4 hours) at 40° C., adding protein A and/or protein G sepharose beads to the cell lysate, incubating for about an hour or more at 40° C., washing the beads in lysis buffer and resuspending the beads in SDS/sample buffer. The ability of the antibody of interest to immunoprecipitate a particular antigen can be assessed by, e.g., western blot analysis. One of skill in the art would be knowledgeable as to the parameters that can be modified to increase the binding of the antibody to an antigen and decrease the background (e.g., pre-clearing the cell lysate with sepharose beads). For further discussion regarding immunoprecipitation protocols see, e.g., Ausubel et al, eds, 1994, Current Protocols in Molecular Biology, Vol. 1, John Wiley & Sons, Inc., New York at 10.16.1.

Western blot analysis generally comprises preparing protein samples, electrophoresis of the protein samples in a polyacrylamide gel (e.g., 8%-20% SDS-PAGE depending on the molecular weight of the antigen), transferring the protein sample from the polyacrylamide gel to a membrane such as nitrocellulose, PVDF or nylon, incubating the membrane in blocking solution (e.g., PBS with 3% BSA or non-fat milk), washing the membrane in washing buffer (e.g., PBS-Tween 20), incubating the membrane with primary antibody (the antibody of interest) diluted in blocking buffer, washing the membrane in washing buffer, incubating the membrane with a secondary antibody (which recognizes the primary antibody, e.g., an anti-human antibody) conjugated to an enzymatic substrate (e.g., horseradish peroxidase or alkaline phosphatase) or radioactive molecule (e.g., ³²P or ¹²⁵I) diluted in blocking buffer, washing the membrane in wash buffer, and detecting the presence of the antigen. One of skill in the art would be knowledgeable as to the parameters that can be modified to increase the signal detected and to reduce the background noise. For further discussion regarding western blot protocols see, e.g., Ausubel et al, eds, 1994, Current Protocols in Molecular Biology, Vol. 1, John Wiley & Sons, Inc., New York at 10.8.1.

Protein expression levels can also be separated by two-dimensional gel electrophoresis systems. Two-dimensional gel electrophoresis is well-known in the art and typically involves iso-electric focusing along a first dimension followed by SDS-PAGE electrophoresis along a second dimension. See, e.g., Hames et al., 1990, Gel Electrophoresis ofproteins: A Practical Approach, IRL Press, New York; Shevchenko et al., 1996, Proc. Natl. Acad. Sci. USA 93:1440-1445; Sagliocco et al., 1996, Yeast 12:1519-1533; Lander, 1996, Science 274:536-539. The resulting electropherograms can be analyzed by numerous techniques, including mass spectrometric techniques, Western blotting and immunoblot analysis using polyclonal and monoclonal antibodies, and internal and N-terminal micro-sequencing.

5.3. Treating CML by Modulating Expression and/or Activity of CML Progression Genes and/or Their Products

The invention provides methods and compositions for utilizing CML target genes listed in Table 3 or 5a or 5b and or imatinib resistance genes listed in Table 4 in treating CML. The methods and compositions are used for treating CML patient exhibiting aberrant regulation of one or more CML target/progression genes or IM resistance genes by modulating the expression and/or activity of such genes and/or the encoded proteins. The methods and composition can be used in conjunction with other CML treatment, e.g., imatinib mesylate. The compositions (e.g., agents that modulate expression and/or activity of the CML target gene or gene product) of the invention are preferably purified. In the following, for simplicity reasons, the methods are often described with reference to CML target gene(s). It will be understood that the methods are equally applicable to CML progression genes and IM resistance genes.

In one embodiment, the invention provides methods and compositions for treating a CML patient exhibiting an aberrant up-regulation of a CML target gene by reducing the expression and/or activity of the gene, and/or its encoded protein by at least 2 fold, 3 fold, 4 fold, 6 fold, 8 fold or 9 fold.

In a specific embodiment, the invention provides methods and compositions for treating a CML patient exhibiting an aberrant up-regulation of a CML target gene as listed in Table 5a or 5b by reducing the expression and/or activity of the gene, and/or its encoded protein.

In another embodiment, the invention provides methods and compositions for treating a CML patient exhibiting an aberrant down-regulation of a CML target gene by enhancing the expression and/or activity of the gene, and/or its encoded protein by at least 2 fold, 3 fold, 4 fold, 6 fold, 8 fold or 9 fold.

In a specific embodiment, the invention provides methods and compositions for treating a CML patient exhibiting an aberrant down-regulation of a CML target gene as listed in Table 5a or 5b by enhancing the expression and/or activity of the gene, and/or its encoded protein.

In a specific embodiment, the invention provides a method for treating CML by administering to a patient (i) an agent that modulates the expression and/or activity of an imatinib resistance gene and/or the encoded protein, and (ii) a therapeutically sufficient amount of imatinib mesylate.

In another embodiment, the invention provides methods and compositions for treating a CML patient exhibiting aberrant regulation of a plurality of different CML target gene as listed in Tables 5a and 5b by modulating the expression and/or activity of the plurality of genes, and/or its encoded proteins. In one embodiment, a CML patient exhibiting aberrant up-regulation of a plurality of CML progression gene listed in Tables 5a and 5b, e.g. 2, 3, 4, 5, 10 or more different CML target genes, is treated by administering to the patient one or more agents that reduce the expression and/or activities of these genes, and/or their encoded proteins.

A variety of therapeutic approaches may be used in accordance with the invention to modulate expression of a CML target gene or imatinib resistance gene and/or its encoded protein in vivo. For example, siRNA molecules may be engineered and used to silence a CML target gene in vivo. Antisense DNA molecules may also be engineered and used to block translation of a CML target mRNA in vivo. Alternatively, ribozyme molecules may be designed to cleave and destroy the mRNAs of a CML target gene in vivo. In another alternative, oligonucleotides designed to hybridize to the 5′ region of the CML target gene (including the region upstream of the coding sequence) and form triple helix structures may be used to block or reduce transcription of the CML target gene. The expression and/or activity of a CML target protein can be modulated using antibody, peptide or polypeptide molecules, and small organic or inorganic molecules. In the following, for simplicity, methods are described in reference to a CML target gene or protein. These methods are equally applicable to imatinib resistance genes.

In a preferred embodiment, RNAi is used to knock down the expression of a CML target gene. In one embodiment, double-stranded RNA molecules of 21-23 nucleotides which hybridize to a homologous region of mRNAs transcribed from the CML target gene are used to degrade the mRNAs, thereby “silence” the expression of the CML target gene. The method can be used to reduce expression levels of aberrantly up-regulated CML target genes. Preferably, the dsRNAs have a hybridizing region, e.g., a 19-nucleotide double-stranded region, which is complementary to a sequence of the coding sequence of the CML target gene. Any siRNA that targets an appropriate coding sequence of a CML target gene and exhibit a sufficient level of silencing can be used in the invention. As exemplary embodiments, 21-nucleotide double-stranded siRNAs targeting the coding regions of a CML target gene are designed according to selection rules known in the art (see, e.g., Elbashir et al., 2002, Methods 26:199-213; International Application No. PCT/US04/35636, filed Oct. 27, 2004, each of which is incorporated herein by reference in its entirety). In a preferred embodiment, the siRNA or siRNAs specifically inhibit the translation or transcription of a CML target protein without substantially affecting the translation or transcription of genes encoding other protein kinases in the same kinase family. In a specific embodiment, siRNAs targeting an up-regulated gene listed in Table 4 are used to silence the respective CML target genes.

The invention also provides methods and compositions for treating a CML patient exhibiting aberrant up-regulation of a plurality of CML target genes as listed in Tables 5a and 5b by reducing the expression and/or activities of these genes, and/or their encoded proteins. In one embodiment, a CML patient exhibiting aberrant up-regulation of a plurality of CML target gene listed in Tables 5a and 5b, e.g. 2, 3, 4, 5, 10 or more different CML target genes, is treated by administering to the patient one or more agents that reduce the expression and/or activities of these genes, and/or their encoded proteins. In a preferred embodiment, an siRNA is used to silence the plurality of different CML target genes. The sequence of the siRNA is chosen such that the transcript of each of the genes comprises a nucleotide sequence that is identical to a central contiguous nucleotide sequence of at least 11 nucleotides of the sense strand or the antisense strand of the siRNA, and/or comprises a nucleotide sequence that is identical to a contiguous nucleotide sequence of at least 9 nucleotides at the 3′ end of the sense strand or the antisense strand of the siRNA. Thus, when administrated to the patient, the siRNA silences all of the plurality of genes in cells of the patient. In preferred embodiments, the central contiguous nucleotide sequence of the siRNA that is identical to one or more CML target genes is 11-15, 14-15, 11, 12, or 13 nucleotides in length. In other preferred embodiments, the 3′ contiguous nucleotide sequence of the siRNA that is identical to one or more CML target genes is 9-15, 9-12, 11, 10, or 9 nucleotides in length. The length and nucleotide base sequence of the target sequence of each different target gene, i.e., the sequence of the gene that is identical to an appropriate sense or antisense sequence of the siRNA, can be different from gene to gene. For example, gene A may have a sequence of 11 nucleotides identical to the nucleotide sequence 3-13 of the sense strand of the siRNA, while gene B may have a sequence of 12 nucleotides identical to the nucleotide sequence 4-15 of the sense strand of the siRNA. Thus, a single siRNA may be designed to silence a large number of CML target genes in cells.

RNAi can be carried out using any standard method for introducing nucleic acids into cells. In one embodiment, gene silencing is induced by presenting the cell with one or more siRNAs targeting the CML target gene (see, e.g., Elbashir et al., 2001, Nature 411, 494-498; Elbashir et al., 2001, Genes Dev. 15, 188-200, all of which are incorporated by reference herein in their entirety). The siRNAs can be chemically synthesized, or derived from cleavage of double-stranded RNA by recombinant Dicer. Another method to introduce a double stranded DNA (dsRNA) for silencing of the CML target gene is shRNA, for short hairpin RNA (see, e.g., Paddison et al., 2002, Genes Dev. 16, 948-958; Brummelkamp et al., 2002, Science 296, 550-553; Sui, G. et al. 2002, Proc. Natl. Acad. Sci. USA 99, 5515-5520, all of which are incorporated by reference herein in their entirety). In this method, a siRNA targeting a CML target gene is expressed from a plasmid (or virus) as an inverted repeat with an intervening loop sequence to form a hairpin structure. The resulting RNA transcript containing the hairpin is subsequently processed by Dicer to produce siRNAs for silencing. Plasmid- or virus-based shRNAs can be expressed stably in cells, allowing long-term gene silencing in cells both in vitro and in vivo (see, McCaffrey et al. 2002, Nature 418, 38-39; Xia et al., 2002, Nat. Biotech. 20, 1006-1010; Lewis et al., 2002, Nat. Genetics 32, 107-108; Rubinson et al., 2003, Nat. Genetics 33, 401-406; Tiscornia et al., 2003, Proc. Natl. Acad. Sci. USA 100, 1844-1848, all of which are incorporated by reference herein in their entirety). Such plasmid- or virus-based shRNAs can be delivered using a gene therapy approach. SiRNAs targeting the CML target gene can also be delivered to an organ or tissue in a mammal, such a human, in vivo (see, e.g., Song et al. 2003, Nat. Medicine 9, 347-351; Sorensen et al., 2003, J Mol. Biol. 327, 761-766; Lewis et al., 2002, Nat. Genetics 32, 107-108, all of which are incorporated by reference herein in their entirety). In this method, a solution of siRNA is injected intravenously into the mammal. The siRNA can then reach an organ or tissue of interest and effectively reduce the expression of the target gene in the organ or tissue of the mammal.

In preferred embodiments, an siRNA pool (mixture) containing at least k (k=2, 3, 4, 5, 6 or 10) different siRNAs targeting a CML target gene at different sequence regions is used to silence the gene. In a preferred embodiment, the total siRNA concentration of the pool is about the same as the concentration of a single siRNA when used individually. As used herein, the word “about” with reference to concentration means within 20%. Preferably, the total concentration of the pool of siRNAs is an optimal concentration for silencing the intended target gene. An optimal concentration is a concentration further increase of which does not increase the level of silencing substantially. In one embodiment, the optimal concentration is a concentration further increase of which does not increase the level of silencing by more than 5%, 10% or 20%. In a preferred embodiment, the composition of the pool, including the number of different siRNAs in the pool and the concentration of each different siRNA, is chosen such that the pool of siRNAs causes less than 30%, 20%, 10% or 5%, 1%, 0.1% or 0.01% of silencing of any off-target genes (e.g., as determined by standard nucleic acid assay, e.g., PCR). In another preferred embodiment, the concentration of each different siRNA in the pool of different siRNAs is about the same. In still another preferred embodiment, the respective concentrations of different siRNAs in the pool are different from each other by less than 5%, 10%, 20% or 50% of the concentration of any one siRNA or said total siRNA concentration of said different siRNAs. In still another preferred embodiment, at least one siRNA in the pool of different siRNAs constitutes more than 90%, 80%, 70%, 50%, or 20% of the total siRNA concentration in the pool. In still another preferred embodiment, none of the siRNAs in the pool of different siRNAs constitutes more than 90%, 80%, 70%, 50%, or 20% of the total siRNA concentration in the pool. In other embodiments, each siRNA in the pool has a concentration that is lower than the optimal concentration when used individually. In a preferred embodiment, each different siRNA in the pool has an concentration that is lower than the concentration of the siRNA that is effective to achieve at least 30%, 50%, 75%, 80%, 85%, 90% or 95% silencing when used in the absence of other siRNAs or in the absence of other siRNAs designed to silence the gene. In another preferred embodiment, each different siRNA in the pool has a concentration that causes less than 30%, 20%, 10% or 5% of silencing of the gene when used in the absence of other siRNAs or in the absence of other siRNAs designed to silence the gene. In a preferred embodiment, each siRNA has a concentration that causes less than 30%, 20%, 10% or 5% of silencing of the target gene when used alone, while the plurality of siRNAs causes at least 80% or 90% of silencing of the target gene. In specific embodiments, a pool containing the 3 different is used for targeting a CML target gene. More detailed descriptions of techniques for carrying out RNAi are also presented in Section 5.6.

In other embodiments, antisense, ribozyme, and triple helix forming nucleic acid are designed to inhibit the translation or transcription of a CML target protein or gene with minimal effects on the expression of other genes that may share one or more sequence motif with the CML target gene. To accomplish this, the oligonucleotides used should be designed on the basis of relevant sequences unique to a CML target gene. In one embodiment, the oligonucleotide used specifically inhibits the translation or transcription of a CML target protein or gene without substantially affecting the translation or transcription of other proteins in the same protein family.

For example, and not by way of limitation, the oligonucleotides should not fall within those regions where the nucleotide sequence of a CML target gene is most homologous to that of other genes. In the case of antisense molecules, it is preferred that the sequence be at least 18 nucleotides in length in order to achieve sufficiently strong annealing to the target mRNA sequence to prevent translation of the sequence. Izant et al., 1984, Cell, 36:1007-1015; Rosenberg et al., 1985, Nature, 313:703-706.

Ribozymes are RNA molecules which possess highly specific endoribonuclease activity. Hammerhead ribozymes comprise a hybridizing region which is complementary in nucleotide sequence to at least part of the target RNA, and a catalytic region which is adapted to cleave the target RNA. The hybridizing region contains nine (9) or more nucleotides. Therefore, the hammerhead ribozymes useful for targeting a CML target gene having a hybridizing region which is complementary to the sequences of the target gene and is at least nine nucleotides in length. The construction and production of such ribozymes is well known in the art and is described more fully in Haseloff et al., 1988, Nature, 334:585-591.

The ribozymes of the present invention also include RNA endoribonucleases (hereinafter “Cech-type ribozymes”) such as the one which occurs naturally in Tetrahymena Thermophila (known as the IVS, or L-19 IVS RNA) and which has been extensively described by Thomas Cech and collaborators (Zaug, et al., 1984, Science, 224:574-578; Zaug and Cech, 1986, Science, 231:470-475; Zaug, et al., 1986, Nature, 324:429-433; published International patent application No. WO 88/04300 by University Patents Inc.; Been et al., 1986, Cell, 47:207-216). The Cech endoribonucleases have an eight base pair active site which hybridizes to a target RNA sequence whereafter cleavage of the target RNA takes place.

In the case of oligonucleotides that hybridize to and form triple helix structures at the 5′ terminus of a CML target gene and can be used to block transcription, it is preferred that they be complementary to those sequences in the 5′ terminus of a CML target gene which are not present in other related genes. It is also preferred that the sequences not include those regions of the promoter of a CML target gene which are even slightly homologous to that of other related genes.

The foregoing compounds can be administered by a variety of methods which are known in the art including, but not limited to the use of liposomes as a delivery vehicle. Naked DNA or RNA molecules may also be used where they are in a form which is resistant to degradation such as by modification of the ends, by the formation of circular molecules, or by the use of alternate bonds including phosphothionate and thiophosphoryl modified bonds. In addition, the delivery of nucleic acid may be by facilitated transport where the nucleic acid molecules are conjugated to poly-lysine or transferrin. Nucleic acid may also be transported into cells by any of the various viral carriers, including but not limited to, retrovirus, vaccinia, AAV, and adenovirus.

Alternatively, a recombinant nucleic acid molecule which encodes, or is, such antisense nucleic acid, ribozyme, triple helix forming nucleic acid, or nucleic acid molecule of a CML target gene can be constructed. This nucleic acid molecule may be either RNA or DNA. If the nucleic acid encodes an RNA, it is preferred that the sequence be operatively attached to a regulatory element so that sufficient copies of the desired RNA product are produced. The regulatory element may permit either constitutive or regulated transcription of the sequence. In vivo, that is, within the cells or cells of an organism, a transfer vector such as a bacterial plasmid or viral RNA or DNA, encoding one or more of the RNAs, may be transfected into cells e.g. (Llewellyn et al., 1987, J. Mol. Biol., 195:115-123; Hanahan et al. 1983, J. Mol. Biol., 166:557-580). Once inside the cell, the transfer vector may replicate, and be transcribed by cellular polymerases to produce the RNA or it may be integrated into the genome of the host cell. Alternatively, a transfer vector containing sequences encoding one or more of the RNAs may be transfected into cells or introduced into cells by way of micromanipulation techniques such as microinjection, such that the transfer vector or a part thereof becomes integrated into the genome of the host cell.

The activity of a CML target protein can be modulated by modulating the interaction of a CML target protein with its binding partners. In one embodiment, agents, e.g., antibodies, peptides, aptamers, small organic or inorganic molecules, can be used to inhibit binding of a CML target protein binding partner to treat CML. In another embodiment, agents, e.g., antibodies, aptamers, small organic or inorganic molecules, can be used to inhibit the activity of a CML target protein to treat CML.

In other embodiments, when the CML target protein is a kinase, the invention provides small molecule inhibitors of the CML target protein. A small molecule inhibitor is a low molecular weight phosphorylation inhibitor. As used herein, a small molecule refers to an organic or inorganic molecule having a molecular weight is under 1000 Daltons, preferably in the range between 300 to 700 Daltons, which is not a nucleic acid molecule or a peptide molecule. The small molecule can be naturally occurring, e.g., extracted from plant or microorganisms, or non-naturally occurring, e.g., generated de novo by synthesis. A small molecule that is an inhibitor can be used to block a cellular process that dependent on a CML target protein. In one embodiment, the inhibitors are substrate Mimics. In a preferred embodiment, the inhibitor of the CML target proteins is an ATP mimic. In one embodiment, such ATP mimics possess at least two aromatic rings. In a preferred embodiment, the ATP mimic comprises a moiety that forms extensive contacts with residues lining the ATP binding cleft of the CML target protein and/or peptide segments just outside the cleft, thereby selectively blocking the ATP binding site of the CML target protein. Minor structural differences from ATP can be introduced into the ATP mimic based on the peptide segments just outside the cleft. Such differences can lead to specific hydrogen bonding and hydrophobic interactions with the peptide segments just outside the cleft.

In still other embodiments, antibodies that specifically bind the CML target protein are used. In a preferred embodiment, the invention provides antibodies that specifically bind the extracellular domain of a CML target protein that is a receptor. Antibodies that specifically bind a target can be obtained using standard method known in the art, e.g., a method described in Section 5.8.

In one embodiment, an antibody-drug conjugate comprising an antibody that specifically binds a CML target protein is used. The efficacy of the antibodies that targets specific molecules expressed by advanced phase immature myeloid cells can be increased by attaching toxins to them. Existing immunotoxins are based on bacterial toxins like pseudomonas exotoxin, plant exotoxin like ricin or radio-nucleotides. The toxins are chemically conjugated to a specific ligand such as the variable domain of the heavy or light chain of the monoclonal antibody. Normal cells lacking the cancer specific antigens are not targeted by the targeted antibody. In a preferred embodiment, the CML target protein target is PRAME.

In other embodiments, a peptide and peptidomimetic that interferes with the interaction of a CML target protein with its interaction partner is used. A peptide preferably has a size of at least 5, 10, 15, 20 or 30 amino acids. Such a peptide or peptidomimetic can be designed by a person skilled in the art based on the sequence and structure of a CML target protein. In one embodiment, a peptide or peptidomimetic that interferes with substrate binding of a CML target protein is used. In another embodiment, peptide or peptidomimetic that interferes with the binding of a signal molecule to a CML target protein is used. In some embodiments of the invention, a fragment or polypeptide of at least 5, 10, 20, 50, 100 amino acids in length of a CML target protein are used. In a specific embodiment, a peptide or peptidomimetic that interferes with the interaction with PRAME is used. The peptide can be prepared by standard method known in the art.

In another embodiment, a dominant negative mutant of a CML target protein is used to reduce activity of a CML target protein. Such a dominant negative mutant can be designed by a person skilled in the art based on the sequence and structure of a CML target protein. In one embodiment, a dominant negative mutant that interferes with substrate binding of a CML target protein is used. In another embodiment, a dominant negative mutant that interferes with the binding of a signal molecule to a CML target protein is used. In a preferred embodiment, the invention provides a dominant negative mutant that comprises the C-terminal region of a CML target protein. In another embodiment, the invention provides a dominant negative mutant that comprises the N-terminal region of the CML target protein.

Gene therapy can be used for delivering any of the above described nucleic acid and protein/peptide therapeutics into target cells. Gene therapy is particularly useful for enhancing aberrantly down-regulated genes. Exemplary methods for carrying out gene therapy are described below. For general reviews of the methods of gene therapy, see Goldspiel et al., 1993, Clinical Pharmacy 12:488-505; Wu and Wu, 1991, Biotherapy 3:87-95; Tolstoshev, 1993, Ann. Rev. Pharmacol. Toxicol. 32:573-596; Mulligan, 1993, Science 260:926-932; and Morgan and Anderson, 1993, Ann. Rev. Biochem. 62:191-217; May, 1993, TIBTECH 11 (5):155-215). Methods commonly known in the art of recombinant DNA technology which can be used are described in Ausubel et al. (eds.), 1993, Current Protocols in Molecular Biology, John Wiley & Sons, New York; and Kriegler, 1990, Gene Transfer and Expression, A Laboratory Manual, Stockton Press, New York.

In a preferred embodiment, the therapeutic comprises a nucleic acid that is part of an expression vector that expresses a the therapeutic nucleic acid or peptide/polypeptide in a suitable host. In particular, such a nucleic acid has a promoter operably linked to the coding region, said promoter being inducible or constitutive, and, optionally, tissue-specific. In another particular embodiment, a nucleic acid molecule is used in which the coding sequences and any other desired sequences are flanked by regions that promote homologous recombination at a desired site in the genome, thus providing for intrachromosomal expression of the CML target nucleic acid (see e.g., Koller and Smithies, 1989, Proc. Natl. Acad. Sci. U.S.A. 86:8932-8935; Zijlstra et al., 1989, Nature 342:435-438).

Delivery of the nucleic acid into a patient may be either direct, in which case the patient is directly exposed to the nucleic acid or nucleic acid-carrying vector, or indirect, in which case, cells are first transformed with the nucleic acid in vitro, then transplanted into the patient. These two approaches are known, respectively, as in vivo or ex vivo gene therapy.

In a specific embodiment, the nucleic acid is directly administered in vivo, where it is expressed to produce the encoded product. This can be accomplished by any of numerous methods known in the art, e.g., by constructing it as part of an appropriate nucleic acid expression vector and administering it so that it becomes intracellular, e.g., by infection using a defective or attenuated retroviral or other viral vector (see U.S. Pat. No. 4,980,286), or by direct injection of naked DNA, or by use of microparticle bombardment (e.g., a gene gun; Biolistic, Dupont), or coating with lipids or cell-surface receptors or transfecting agents, encapsulation in liposomes, microparticles, or microcapsules, or by administering it in linkage to a peptide which is known to enter the nucleus, by administering it in linkage to a ligand subject to receptor-mediated endocytosis (see e.g., Wu and Wu, 1987, J. Biol. Chem. 262:4429-4432) (which can be used to target cell types specifically expressing the receptors), etc. In another embodiment, a nucleic acid-ligand complex can be formed in which the ligand comprises a fusogenic viral peptide to disrupt endosomes, allowing the nucleic acid to avoid lysosomal degradation. In yet another embodiment, the nucleic acid can be targeted in vivo for cell specific uptake and expression, by targeting a specific receptor (see, e.g., PCT Publications WO 92/06180 dated Apr. 16, 1992 (Wu et al.); WO 92/22635 dated Dec. 23, 1992 (Wilson et al.); WO92/20316 dated Nov. 26, 1992 (Findeis et al.); WO93/14188 dated Jul. 22, 1993 (Clarke et al.), WO 93/20221 dated Oct. 14, 1993 (Young)). Alternatively, the nucleic acid can be introduced intracellularly and incorporated within host cell DNA for expression, by homologous recombination (Koller and Smithies, 1989, Proc. Natl. Acad. Sci. U.S.A. 86:8932-8935; Zijlstra et al., 1989, Nature 342:435-438).

In a specific embodiment, a viral vector that contains the nucleic acid of a CML target gene is used. For example, a retroviral vector can be used (see Miller et al., 1993, Meth. Enzymol. 217:581-599). These retroviral vectors have been modified to delete retroviral sequences that are not necessary for packaging of the viral genome and integration into host cell DNA. The CML target nucleic acid to be used in gene therapy is cloned into the vector, which facilitates delivery of the gene into a patient. More detail about retroviral vectors can be found in Boesen et al., 1994, Biotherapy 6:291-302, which describes the use of a retroviral vector to deliver the mdrl gene to hematopoietic stem cells in order to make the stem cells more resistant to chemotherapy. Other references illustrating the use of retroviral vectors in gene therapy are: Clowes et al., 1994, J. Clin. Invest. 93:644-651; Kiem et al., 1994, Blood 83:1467-1473; Salmons and Gunzberg, 1993, Human Gene Therapy 4:129-141; and Grossman and Wilson, 1993, Curr. Opin. Genet. and Devel. 3:110-114.

Adenoviruses are other viral vectors that can be used in gene therapy. Adenoviruses are especially attractive vehicles for delivering genes to respiratory epithelia. Adenoviruses naturally infect respiratory epithelia where they cause a mild disease. Other targets for adenovirus-based delivery systems are liver, the central nervous system, endothelial cells, and muscle. Adenoviruses have the advantage of being capable of infecting non-dividing cells. Kozarsky and Wilson (1993, Current Opinion in Genetics and Development 3:499-503) present a review of adenovirus-based gene therapy. Bout et al. (1994, Human Gene Therapy 5:3-10) demonstrated the use of adenovirus vectors to transfer genes to the respiratory epithelia of rhesus monkeys. Other instances of the use of adenoviruses in gene therapy can be found in Rosenfeld et al., 1991, Science 252:431-434; Rosenfeld et al., 1992, Cell 68:143-155; and Mastrangeli et al., 1993, J. Clin. Invest. 91:225-234.

Adeno-associated virus (AAV) has also been proposed for use in gene therapy (Walsh et al., 1993, Proc. Soc. Exp. Biol. Med. 204:289-300).

Another approach to gene therapy involves transferring a gene to cells in tissue culture by such methods as electroporation, lipofection, calcium phosphate mediated transfection, or viral infection. Usually, the method of transfer includes the transfer of a selectable marker to the cells. The cells are then placed under selection to isolate those cells that have taken up and are expressing the transferred gene. Those cells are then delivered to a patient.

In this embodiment, the nucleic acid is introduced into a cell prior to administration in vivo of the resulting recombinant cell. Such introduction can be carried out by any method known in the art, including but not limited to transfection, electroporation, microinjection, infection with a viral or bacteriophage vector containing the nucleic acid sequences, cell fusion, chromosome-mediated gene transfer, microcell-mediated gene transfer, spheroplast fusion, etc. Numerous techniques are known in the art for the introduction of foreign genes into cells (see e.g., Loeffler and Behr, 1993, Meth. Enzymol. 217:599-618; Cohen et al., 1993, Meth. Enzymol. 217:618-644; Cline, 1985, Pharmac. Ther. 29:69-92) and may be used in accordance with the present invention, provided that the necessary developmental and physiological functions of the recipient cells are not disrupted. The technique should provide for the stable transfer of the nucleic acid to the cell, so that the nucleic acid is expressible by the cell and preferably heritable and expressible by its cell progeny.

The resulting recombinant cells can be delivered to a patient by various methods known in the art. In a preferred embodiment, epithelial cells are injected, e.g., subcutaneously. In another embodiment, recombinant skin cells may be applied as a skin graft onto the patient. Recombinant blood cells (e.g., hematopoietic stem or progenitor cells) are preferably administered intravenously. The amount of cells envisioned for use depends on the desired effect, patient state, etc., and can be determined by one skilled person in the art.

Cells into which a nucleic acid can be introduced for purposes of gene therapy encompass any desired, available cell type, and include but are not limited to epithelial cells, endothelial cells, keratinocytes, fibroblasts, muscle cells, hepatocytes; blood cells such as T lymphocytes, B lymphocytes, monocytes, macrophages, neutrophils, eosinophils, megakaryocytes, granulocytes; various stem or progenitor cells, in particular hematopoietic stem or progenitor cells, e.g., as obtained from bone marrow, umbilical cord blood, peripheral blood, fetal liver, etc.

In a preferred embodiment, the cell used for gene therapy is autologous to the patient.

In an embodiment in which recombinant cells are used in gene therapy, a nucleic acid is introduced into the cells such that it is expressible by the cells or their progeny, and the recombinant cells are then administered in vivo for therapeutic effect. In a specific embodiment, stem or progenitor cells are used. Such stem cells can be hematopoietic stem cells (HSC).

Any technique which provides for the isolation, propagation, and maintenance in vitro of HSC can be used in this embodiment of the invention. Techniques by which this may be accomplished include (a) the isolation and establishment of HSC cultures from bone marrow cells isolated from the future host, or a donor, or (b) the use of previously established long-term HSC cultures, which may be allogeneic or xenogeneic. Non-autologous HSC are used preferably in conjunction with a method of suppressing transplantation immune reactions of the future host/patient. In a particular embodiment of the present invention, human bone marrow cells can be obtained from the posterior iliac crest by needle aspiration (see e.g., Kodo et al., 1984, J. Clin. Invest. 73:1377-1384). The HSCs can be made highly enriched or in substantially pure form. This enrichment can be accomplished before, during, or after long-term culturing, and can be done by any techniques known in the art. Long-term cultures of bone marrow cells can be established and maintained by using, for example, modified Dexter cell culture techniques (Dexter et al., 1977, J. Cell Physiol. 91:335) or Witlock-Witte culture techniques (Witlock and Witte, 1982, Proc. Natl. Acad. Sci. U.S.A. 79:3608-3612).

In a specific embodiment, the nucleic acid to be introduced for purposes of gene therapy comprises an inducible promoter operably linked to the coding region, such that expression of the nucleic acid is controllable by controlling the presence or absence of the appropriate inducer of transcription.

The methods and/or compositions described above for modulating the expression and/or activity of a CML target gene or CML target protein may be used to treat patients in conjunction with a chemotherapeutic agent, e.g., Gleevec™.

The effects or benefits of administration of the compositions of the invention alone or in conjunction with a chemotherapeutic agent can be evaluated by any methods known in the art, e.g., by methods that are based on measuring the survival rate, side effects, dosage requirement of the chemotherapeutic agent, or any combinations thereof. If the administration of the compositions of the invention achieves any one or more benefits in a patient, such as increasing the survival rate, decreasing side effects, lowing the dosage requirement for the chemotherapeutic agent, the compositions of the invention are said to have augmented a chemotherapy, and the method is said to have efficacy.

5.4. Diagnosis and Treatment of CML by Targeting Cell Surface Expressed PRAME

The present invention provides methods and compositions for diagnosis and treatment of CML by targeting PRAME (GenBank® accession no. NM_(—)006115) on cell surfaces of advanced phase hematopoetic stem cells and immature myeloid cells. PRAME is known to be expressed in testis and to expressed at a low level in endometrium, adrenals and ovaries, and is not expressed in other normal tissues. The inventors have found that PRAME is significantly overexpressed in advanced phase CML cells as compared to chronic phase CML cells. Thus, methods and compositions that target PRAME can be used for detecting advanced phase CML cells and for treating CML by selectively targeting advanced phase CML cells.

5.4.1. Methods of Detecting Advanced Phase CML

Antibodies or labeled antibodies directed against a PRAME (Preferentially Expressed Antigen of Melanoma) can be used for evaluating CML progression, e.g., by detecting the presence of PRAME protein on cell surface of hematopoetic stem cells and immature myeloid cells. Such diagnostic/prognostic methods are particularly useful for detecting CML progression in unsorted samples.

The tissue or cell type to be analyzed may include those which are known to relate to CML, e.g., bone marrow or peripheral blood. The protein isolation methods employed herein may, for example, be such as those described in Harlow and Lane (Harlow, E. and Lane, D., 1988, “Antibodies: A Laboratory Manual”, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.), which is incorporated herein by reference in its entirety. The isolated cells can be derived from cell culture or from a patient. The analysis of cells taken from culture may be a necessary step in the assessment of cells to be used as part of a cell-based gene therapy technique or, alternatively, to test the effect of compounds for CML treatment.

In one embodiment, the invention provides a method for diagnosing whether a patient has advanced phase chronic myeloid leukemia (CML), comprising (a) contacting a cell sample from said patient with an antibody conjugate, said antibody conjugate comprising an antibody that binds a PRAME protein conjugated with a label; and (b) detecting said label in said sample, wherein detection of said label above a predetermined threshold indicating said patient has advanced phase CML. Detection of the labeled antibody can be performed using a method described in Section 5.2.5, supra.

5.4.2. Methods of Treating CML by Targeting PRAME

The invention provides methods and compositions for treating CML by targeting PRAME expressed on the cell surface.

In one embodiment, the present invention provides methods of using anti-PRAME antibodies for treatment of a CML patient. In the methods of the invention, one or more anti-PRAME antibodies are administered to the patient. The anti-PRAME antibodies bind to PRAME on the surface of advanced phase CML hematopoetic stem cells and/or immature myeloid cells. The binding of arti-PRAME antibodies to PRAME blocks the function mediated by PRAME, thereby preventing the proliferation of advanced phase hematopoetic stem cells.

In another embodiment, the present invention provides a method for treatment of CML using an anti-PRAME antibody that belongs to an isotype that is capable of mediating lysis of cells to which the anti-PRAME antibody is bound. In a preferred embodiment, the anti-PRAME antibody belongs to an isotype that binds a growth factor receptor and activates serum complement and/or mediates antibody dependent cellular cytotoxicity (ADCC) by activating effector cells, e.g., macrophages. In another preferred embodiment, the isotype is IgG1, IgG2a, IgG3 or IgM.

In still another embodiment, the anti-PRAME antibodies are used in conjunction with one or more other chemotherapeutic drugs. In such combined therapies, the anti-PRAME antibodies can be administered in a manner such as described in Section 5.10.5.

The dosage of the anti-PRAME antibodies can be determined by routine experiments that are familiar to one skilled in the art. The effects or benefits of administration of the anti-PRAME antibodies can be evaluated by any method known in the art.

In another embodiment, an antibody-drug conjugate comprising an antibody that specifically binds PRAME and a chemotherapeutic drug is used to selectively deliver the chemotherapeutic drug to advanced phase CML hematopoetic stem cells and/or immature myeloid cells. Chemotherapeutic drugs normally spread throughout the body, reaching not only the intended target but also healthy cells/organs such as the intestines and healthy bone marrow, where they kill off normal dividing cells. A drug conjugated to PRAME should be able to selectively target the advance phase CML hematopoetic stem cells and/or immature myeloid cells, thus increasing the sensitivity and specificity of the drug. For example, an anti-PRAME antibody may be conjugated to a therapeutic moiety such as a cytotoxin, e.g., a cytostatic or cytocidal agent, or a radioactive metal ion (see, e.g., Section 5.8). Any suitable antibody-drug conjugate, e.g., those described in Section 5.8.3 can be used. Normal hematopoetic stem cells and/or myeloid cells lack PRAME and are not targeted by the antibody.

In still another embodiment, a peptide or a peptidomimetic that interferes with the interaction of PRAME with its interaction partner is used. A peptide preferably has a size of at least 5, 10, 15, 20 or 30 amino acids. Such a peptide or peptidomimetic can be designed by a person skilled in the art based on the sequence and structure of PRAME. In some embodiments of the invention, a PRAME fragment of at least 5, 10, 20, 50, 100 amino acids in length is used. In a specific embodiment, a peptide or peptidomimetic that interferes with the interaction with PRAME is used. The peptide can be prepared by a standard method known in the art (see, e.g., Section 5.8.4).

The invention also provides methods for treating CML using fragments of a PRAME protein as vaccines to elicit an immunotherapeutic response in a patient, e.g., an antibody response and/or a cell mediated immune response. Antibody responses involve the production of antibodies, which are proteins called immunoglobulins. The antibodies circulate in the bloodstream and permeate the other body fluids, where they bind specifically to the foreign antigen that elicited them. Binding by antibody inactivates advanced phase CML hematopoetic stem cells and/or immature myeloid cells by blocking their functions facilitated by PRAME. Antibody binding also marks advanced phase CML hematopoetic stem cells and/or immature myeloid cells, either by making it easier for a phagocytic cell to ingest them or by activating a system of blood proteins, collectively called complement, which kills the marked target cells.

Cell-mediated immune responses to PRAME involve the production of specialized cells that react with PRAME antigen on the surface of advanced phase CML cells. T lymphocytes, which develop in the thymus, are responsible for cell-mediated immunity. The majority of T lymphocytes, called helper T cells and suppressor T cells, play a regulatory role in immunity, acting either to enhance or suppress the responses of other white blood cells. Other T lymphocytes, called cytotoxic T cells (CTLs), kill virus-infected cells, parasites, and cancer cells. The surface of T cells contains transmembrane proteins called T cell receptors that recognize the PRAME antigen on the surface of PRAME presenting advanced phase CML cells. T cell receptors are antibody-like proteins. The antigen must be presented to the T cell by a particular membrane protein, one encoded by a complex of genes called the major histocompatibility complex (MHC). Histocompatibility molecules are expressed on the cells of all higher vertebrates. There are two principal classes of MHC molecules, class I MHC and class II MHC. Cytotoxic T lymphocytes (CTLs) recognize foreign antigens in association with class I MHC glycoproteins on the surface of an antigen-presenting cell, whereas helper T cells recognize foreign antigens in association with class II MHC glycoproteins on the surface of an antigen-presenting cell. A cytotoxic T lymphocyte will kill an antigen-presenting cell when it recognizes antigen bound to class I MHC molecules on the surface of the antigen-presenting cell. In one embodiment, a PRAME vaccine is used to elicit production of CTLs.

The PRAME protein fragment or polypeptide can be prepared by a standard method known in the art. In a specific embodiment, the fragment is a human PRAME protein fragment, or its murine homolog. In another embodiment, the vaccine comprises a peptide sequence that is at least 30%, 50%, 70%, 90%, or 95% homologous (e.g., over an equal size) to such fragments of a PRAME protein, e.g., as determined by a BLAST algorithm. In some embodiments, the PRAME protein fragments or polypeptides are at least 5, 10, 20, 50, 100 amino acids in length.

A peptide or polypeptide which is functionally equivalent to any PRAME fragment described above can also be used. Such an equivalent PRAME fragment may contain deletions, additions or substitutions of amino acid residues within the amino acid sequence encoded by the PRAME gene sequence but which result in a silent change, thus producing a functionally equivalent PRAME protein fragment. Amino acid substitutions may be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity, and/or the amphipathic nature of the residues involved. Conservative substitutions may be made from among amino acids of the same polarity. For example, nonpolar (hydrophobic) amino acids include alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan, and methionine; polar neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine, and glutamine; positively charged (basic) amino acids include arginine, lysine, and histidine; and negatively charged (acidic) amino acids include aspartic acid and glutamic acid. “Functionally equivalent”, as utilized herein, refers to a protein fragment capable of exhibiting a substantially similar in vivo activity as the endogenous PRAME protein fragment.

The PRAME peptide fragments may be produced by recombinant DNA technology using techniques well known in the art (see, e.g., Section 5.8.4).

The PRAME peptide can be used in combination with a suitable carrier and/or adjuvant, such as Freund's complete or incomplete adjuvant, or a similar immunostimulatory agent. An oil/surfactant based adjuvant comprising one or more surfactants combined with one or more non-metabolizable mineral oil or metabolizable oil, such as the Incomplete Seppic Adjuvant (Seppic, Paris, France), may be used. An Incomplete Seppic Adjuvant has a comparable effect as Incomplete Freund's Adjuvant for antibody production, but induces a lower inflammatory response.

A fragment of a PRAME gene can also be used as a DNA or RNA vaccine. In a specific embodiment, the fragment of a PRAME gene is a fragment of a human PRAME gene, or its murine homolog. The invention also provides any sequence that is at least 30%, 50%, 70%, 90%, or 95% homologous (e.g., over an equal size) to such fragments of a PRAME gene. In some embodiments of the invention, the fragment of a PRAME gene is at least 20, 25, 40, 60, 80, 100, 500, 1000 bases in length. Such sequences may be useful for production of PRAME peptides.

In another embodiment, the present invention provides a naked DNA or RNA vaccine comprising a fragment of a PRAME gene, and uses thereof. The PRAME DNA fragment can be administered as a vaccine to elicit anti-PRAME antibodies. The DNA can be converted to RNA for example by subcloning the DNA into a transcriptional vector, such as pGEM family of plasmid vectors, or under control of a transcriptional promoter of a virus such as vaccinia, and the RNA used as a naked RNA vaccine. The naked DNA or RNA vaccine can be injected alone, or combined with one or more DNA or RNA vaccines directed to PRAME.

The naked DNA or RNA vaccine of the present invention can be administered for example intramuscularly, or alternatively, can be used in nose drops. The DNA or RNA fragment or a portion thereof can be injected as naked DNA or RNA, as DNA or RNA encapsulated in liposomes, as DNA or RNA entrapped in proteoliposomes containing viral envelope receptor proteins (Nicolau, C. et al. Proc. Natl. Acad. Sci. U.S.A. 1983, 80, 1068; Kanoda, Y., et al. Science 1989, 243, 375; Mannino, R. J. et al. Biotechniques 1988, 6, 682). Alternatively, the DNA can be injected along with a carrier. A carrier can be a protein or such as a cytokine, for example interleukin 2, or a polylysine-glycoprotein carrier (Wu, G. Y. and Wu, C. H. J. Biol. Chem. 1988, 263, 14621), or a nonreplicating vector, for example expression vectors containing either the Rous sarcoma virus or cytomegalovirus promoters. Such carrier proteins and vectors and methods for using same are known to a person in the art (See for example, Acsadi, G. et al. Nature 1991, 352, 815-818). In addition, the DNA or RNA could be coated onto tiny gold beads and the beads introduced into the skin with, for example, a gene gun (Cohen, J. Science 1993, 259, 1691-1692; Ulmer, J. B. et al. Science 1993, 259, 1745-1749).

5.4.3. Depletion of Advanced Phase CML Hematopoetic Stem Cells and/or Immature Myeloid Cells In Vitro

The invention provides methods of depleting advanced phase CML hematopoetic stem cells and/or immature myeloid cells from bone marrow or blood in vitro (or ex vivo). In particular, the invention provides for methods of depleting advanced phase CML hematopoetic stem cells and/or immature myeloid cells by killing them or by separating them from bone marrow or blood. In one embodiment, anti-PRAME antibodies are combined, e.g., incubated, in vitro with bone marrow or blood from a patient, e.g., a human.

In one embodiment, a column containing an anti-PRAME antibody bound to a solid matrix is used to remove advanced phase hematopoetic stem cells and/or immature myeloid cells from a bone marrow or blood sample.

The anti-PRAME antibodies used in the in vitro depletion of advanced phase CML hematopoetic stem cells and/or immature myeloid cells from samples can be conjugated to detectable labels (e.g., various enzymes, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials) or therapeutic agents (e.g., cytostatic and cytocidal agents), which are disclosed in section 5.8.3.

Anti-PRAME antibodies conjugated to detectable substances can be utilized to sort advanced phase hematopoetic stem cells and/or immature myeloid cells from bone marrow or peripheral blood samples by methods known to those of skill in the art. In one embodiment, advanced phase hematopoetic stem cells and/or immature myeloid cells are sorted using a fluorescence activated cell sorter (FACS). Fluorescence activated cell sorting (FACS) is a well-known method for separating particles, including cells, based on the fluorescent properties of the particles (Kamarch, 1987, Methods Enzymol, 151:150-165). Laser excitation of fluorescent moieties in the individual particles results in a small electrical charge allowing electromagnetic separation of positive and negative particles from a mixture.

In one embodiment, bone marrow or peripheral blood samples, obtained from a patient, e.g., a human, are incubated with fluorescently labeled PRAME specific antibodies for a time sufficient to allow the labeled antibodies to bind to the cells. In an alternative embodiment, such cells are incubated with PRAME specific antibodies, the cells are washed, and the cells are incubated with a second labeled antibody that recognizes the PRAME specific antibodies. In accordance with these embodiments, the cells are washed and processed through the cell sorter, allowing separation of cells that bind both antibodies to be separated from hybrid cells that do not bind both antibodies. FACS sorted particles may be directly deposited into individual wells of 96-well or 384-well plates to facilitate separation.

In another embodiment, magnetic beads can be used to separate advanced phase immature myeloid cells from bone marrow or peripheral blood samples. Advanced phase immature myeloid cells may be sorted using a magnetic activated cell sorting (MACS) technique, a method for separating particles based on their ability to bind magnetic beads (0.5-100 nm diameter) (Dynal, 1995). A variety of useful modifications can be performed on the magnetic microspheres, including covalent addition of antibody which immunospecifically recognizes PRAME. A magnetic field is then applied, to physically manipulate the selected beads. The beads are then mixed with the cells to allow binding. Cells are then passed through a magnetic field to separate out advanced phase CML hematopoetic stem cells and/or immature myeloid cells.

Bone marrow or peripheral blood sample from a patient that is depleted of advanced phase CML hematopoetic stem cells and/or immature myeloid cells can be used for autologous transplant treatment of the patient. Healthy bone marrow or peripheral blood cells from a sample depleted of advanced phase CML hematopoetic stem cells and/or immature myeloid cells can be collected. These cells can then be administered to the patient to replace the abnormal cells in the patient's bone marrow. Healthy bone marrow or peripheral blood cells can also be stored, e.g., frozen, for transplant at a later time.

5.5. Methods for Screening Agents That Modulate CML Progression/Target or IM Resistance Proteins

Agents that modulate the expression or activity of a CML progression/target gene or encoded protein (or imatinib resistance gene or encoded protein), or modulate interaction of a CML progression/target protein (or imatinib resistance protein) with other proteins or molecules can be identified using a method described in this section. Such agents are useful in treating CML patients who exhibit aberrant regulation of these genes. In the following, for simplicity, methods directed to CML progression/target gene are described. These methods are equally applicable to imatinib resistance genes.

5.5.1. Screening Assays

The following assays are designed to identify compounds that bind to a CML progression gene or its products, bind to other cellular proteins that interact with a CML progression protein, bind to cellular constituents, e.g., proteins, that are affected by a CML progression protein, or bind to compounds that interfere with the interaction of the CML progression gene or its product with other cellular proteins and to compounds which modulate the expression or activity of a CML progression gene (i.e., modulate the expression level of the CML progression gene and/or modulate the activity level of the CML progression protein). Assays may additionally be utilized which identify compounds which bind to CML progression protein regulatory sequences (e.g., promoter sequences), see e.g., Platt, K. A., 1994, J. Biol. Chem. 269:28558-28562, which is incorporated herein by reference in its entirety, which may modulate the level of CML progression gene expression. Compounds may include, but are not limited to, small organic molecules which are able to affect expression of the CML progression gene or some other gene involved in the CML progression protein pathways, or other cellular proteins. Further, among these compounds are compounds which affect the level of CML progression gene expression and/or CML progression protein activity and which can be used in the regulation of sensitivity to the effect of a chemotherapy agent.

Compounds may include, but are not limited to, peptides such as, for example, soluble peptides, including but not limited to, Ig-tailed fusion peptides, and members of random peptide libraries (see, e.g., Lam, K. S. et al., 1991, Nature 354:82-84; Houghten, R. et al., 1991, Nature 354:84-86), and combinatorial chemistry-derived molecular library made of D- and/or L-configuration amino acids, phosphopeptides (including, but not limited to members of random or partially degenerate, directed phosphopeptide libraries; see, e.g., Songyang, Z. et al., 1993, Cell 72:767-778), antibodies (including, but not limited to, polyclonal, monoclonal, humanized, anti-idiotypic, chimeric or single chain antibodies, and Fab, F(ab′)₂ and Fab expression library fragments, and epitope-binding fragments thereof), and small organic or inorganic molecules.

Compounds identified via assays such as those described herein may be useful, for example, in modulating the biological function of the CML progression protein.

In vitro systems may be designed to identify compounds capable of binding a CML progression protein. Compounds identified may be useful, for example, in modulating the activity of wild type and/or mutant CML progression protein, may be useful in elaborating the biological function of the CML progression protein, may be utilized in screens for identifying compounds that disrupt normal CML progression protein interactions, or may in themselves disrupt such interactions.

The principle of the assays used to identify compounds that bind to the CML progression protein involves preparing a reaction mixture of the CML progression protein and the test compound under conditions and for a time sufficient to allow the two components to interact and bind, thus forming a complex which can be removed and/or detected in the reaction mixture. These assays can be conducted in a variety of ways. For example, one method to conduct such an assay would involve anchoring CML progression protein or the test substance onto a solid phase and detecting CML progression protein/test compound complexes anchored on the solid phase at the end of the reaction. In one embodiment of such a method, the CML progression protein may be anchored onto a solid surface, and the test compound, which is not anchored, may be labeled, either directly or indirectly.

In practice, microtiter plates may conveniently be utilized as the solid phase. The anchored component may be immobilized by non-covalent or covalent attachments. Non-covalent attachment may be accomplished by simply coating the solid surface with a solution of the protein and drying. Alternatively, an immobilized antibody, preferably a monoclonal antibody, specific for the protein to be immobilized may be used to anchor the protein to the solid surface. The surfaces may be prepared in advance and stored.

In order to conduct the assay, the nonimmobilized component is added to the coated surface containing the anchored component. After the reaction is complete, unreacted components are removed (e.g., by washing) under conditions such that any complexes formed will remain immobilized on the solid surface. The detection of complexes anchored on the solid surface can be accomplished in a number of ways. Where the previously nonimmobilized component is pre-labeled, the detection of label immobilized on the surface indicates that complexes were formed. Where the previously nonimmobilized component is not pre-labeled, an indirect label can be used to detect complexes anchored on the surface; e.g., using a labeled antibody specific for the previously nonimmobilized component (the antibody, in turn, may be directly labeled or indirectly labeled with a labeled anti-Ig antibody).

Alternatively, a reaction can be conducted in a liquid phase, the reaction products separated from unreacted components, and complexes detected; e.g., using an immobilized antibody specific for a CML progression protein or the test compound to anchor any complexes formed in solution, and a labeled antibody specific for the other component of the possible complex to detect anchored complexes.

The CML progression gene or CML progression protein may interact in vivo with one or more intracellular or extracellular molecules, such as proteins. For purposes of this discussion, such molecules are referred to herein as “binding partners”. Compounds that disrupt CML progression protein binding may be useful in modulating the activity of the CML progression protein. Compounds that disrupt CML progression gene binding may be useful in modulating the expression of the CML progression gene, such as by modulating the binding of a regulator of CML progression gene. Such compounds may include, but are not limited to molecules such as peptides which would be capable of gaining access to the CML progression protein.

The basic principle of the assay systems used to identify compounds that interfere with the interaction between the CML progression protein and its intracellular or extracellular binding partner or partners involves preparing a reaction mixture containing the CML progression protein, and the binding partner under conditions and for a time sufficient to allow the two to interact and bind, thus forming a complex. In order to test a compound for inhibitory activity, the reaction mixture is prepared in the presence and absence of the test compound. The test compound may be initially included in the reaction mixture, or may be added at a time subsequent to the addition of a CML progression protein and its binding partner. Control reaction mixtures are incubated without the test compound or with a placebo. The formation of any complexes between the CML progression protein and the binding partner is then detected. The formation of a complex in the control reaction, but not in the reaction mixture containing the test compound, indicates that the compound interferes with the interaction of the CML progression protein and the interactive binding partner. Additionally, complex formation within reaction mixtures containing the test compound and a normal CML progression protein may also be compared to complex formation within reaction mixtures containing the test compound and a mutant CML progression protein. This comparison may be important in those cases where it is desirable to identify compounds that disrupt interactions of mutant but not the normal CML progression protein.

The assay for compounds that interfere with the interaction of the CML progression proteins and binding partners can be conducted in a heterogeneous or homogeneous format. Heterogeneous assays involve anchoring either the CML progression protein or the binding partner onto a solid phase and detecting complexes anchored on the solid phase at the end of the reaction. In homogeneous assays, the entire reaction is carried out in a liquid phase. In either approach, the order of addition of reactants can be varied to obtain different information about the compounds being tested. For example, test compounds that interfere with the interaction between the CML progression proteins and the binding partners, e.g., by competition, can be identified by conducting the reaction in the presence of the test substance; i.e., by adding the test substance to the reaction mixture prior to or simultaneously with the CML progression protein and interactive binding partner. Alternatively, test compounds that disrupt preformed complexes, e.g. compounds with higher binding constants that displace one of the components from the complex, can be tested by adding the test compound to the reaction mixture after complexes have been formed. The various formats are described briefly below.

In a heterogeneous assay system, either the CML progression protein or its interactive binding partner, is anchored onto a solid surface, while the non-anchored species is labeled, either directly or indirectly. In practice, microtiter plates are conveniently utilized. The anchored species may be immobilized by non-covalent or covalent attachments. Non-covalent attachment may be accomplished simply by coating the solid surface with a solution of the CML progression protein or binding partner and drying. Alternatively, an immobilized antibody specific for the species to be anchored may be used to anchor the species to the solid surface. The surfaces may be prepared in advance and stored.

In order to conduct the assay, the partner of the immobilized species is exposed to the coated surface with or without the test compound. After the reaction is complete, unreacted components are removed (e.g., by washing) and any complexes formed will remain immobilized on the solid surface. The detection of complexes anchored on the solid surface can be accomplished in a number of ways. Where the non-immobilized species is pre-labeled, the detection of label immobilized on the surface indicates that complexes were formed. Where the non-immobilized species is not pre-labeled, an indirect label can be used to detect complexes anchored on the surface; e.g., using a labeled antibody specific for the initially non-immobilized species (the antibody, in turn, may be directly labeled or indirectly labeled with a labeled anti-Ig antibody). Depending upon the order of addition of reaction components, test compounds which inhibit complex formation or which disrupt preformed complexes can be detected.

Alternatively, the reaction can be conducted in a liquid phase in the presence or absence of the test compound, the reaction products separated from unreacted components, and complexes detected; e.g., using an immobilized antibody specific for one of the binding components to anchor any complexes formed in solution, and a labeled antibody specific for the other partner to detect anchored complexes. Again, depending upon the order of addition of reactants to the liquid phase, test compounds which inhibit complex or which disrupt preformed complexes can be identified.

In an alternative embodiment of the invention, a homogeneous assay can be used. In this approach, a preformed complex of the CML progression protein and the interactive binding partner is prepared in which either the CML progression protein or its binding partners is labeled, but the signal generated by the label is quenched due to complex formation (see, e.g., U.S. Pat. No. 4,109,496 which utilizes this approach for immunoassays). The addition of a test substance that competes with and displaces one of the species from the preformed complex will result in the generation of a signal above background. In this way, test substances which disrupt CML progression protein/binding partner interaction can be identified.

In a particular embodiment, the CML progression protein can be prepared for immobilization using recombinant DNA techniques. For example, the coding region of CML progression gene can be fused to a glutathione-S-transferase (GST) gene using a fusion vector, such as pGEX-5X-1, in such a manner that its binding activity is maintained in the resulting fusion protein. The interactive binding partner can be purified and used to raise a monoclonal antibody, using methods routinely practiced in the art. This antibody can be labeled with the radioactive isotope ¹²⁵I, for example, by methods routinely practiced in the art. In a heterogeneous assay, e.g., the GST-CML progression protein fusion protein can be anchored to glutathione-agarose beads. The interactive binding partner can then be added in the presence or absence of the test compound in a manner that allows interaction and binding to occur. At the end of the reaction-period, unbound material can be washed away, and the labeled monoclonal antibody can be added to the system and allowed to bind to the complexed components. The interaction between the CML progression protein and the interactive binding partner can be detected by measuring the amount of radioactivity that remains associated with the glutathione-agarose beads. A successful inhibition of the interaction by the test compound will result in a decrease in measured radioactivity.

Alternatively, the GST-CML progression protein fusion protein and the interactive binding partner can be mixed together in liquid in the absence of the solid glutathione-agarose beads. The test compound can be added either during or after the species are allowed to interact. This mixture can then be added to the glutathione-agarose beads and unbound material is washed away. Again the extent of inhibition of the CML progression protein/binding partner interaction can be detected by adding the labeled antibody and measuring the radioactivity associated with the beads.

In another embodiment of the invention, these same techniques can be employed using peptide fragments that correspond to the binding domains of the CML progression protein and/or the interactive binding partner (in cases where the binding partner is a protein), in place of one or both of the full length proteins. Any number of methods routinely practiced in the art can be used to identify and isolate the binding sites. These methods include, but are not limited to, mutagenesis of the gene encoding one of the proteins and screening for disruption of binding in a co-immunoprecipitation assay. Compensating mutations in the gene encoding the second species in the complex can then be selected. Sequence analysis of the genes encoding the respective proteins will reveal the mutations that correspond to the region of the protein involved in interactive binding. Alternatively, one protein can be anchored to a solid surface using methods described in this section above, and allowed to interact with and bind to its labeled binding partner, which has been treated with a proteolytic enzyme, such as trypsin. After washing, a short, labeled peptide comprising the binding domain may remain associated with the solid material, which can be isolated and identified by amino acid sequencing. Also, once the gene coding for the binding partner is obtained, short gene segments can be engineered to express peptide fragments of the protein, which can then be tested for binding activity and purified or synthesized.

For example, and not by way of limitation, a CML progression protein can be anchored to a solid material as described in this section, above, by making a GST-CML progression protein fusion protein and allowing it to bind to glutathione agarose beads. The interactive binding partner can be labeled with a radioactive isotope, such as ³⁵S, and cleaved with a proteolytic enzyme such as trypsin. Cleavage products can then be added to the anchored GST-CML progression protein fusion protein and allowed to bind. After washing away unbound peptides, labeled bound material, representing the binding partner binding domain, can be eluted, purified, and analyzed for amino acid sequence by well-known methods. Peptides so identified can be produced synthetically or fused to appropriate facilitative proteins using recombinant DNA technology.

Some CML progression proteins are kinases. Kinase activity of a CML progression protein can be assayed in vitro using a synthetic peptide substrate of a CML progression protein of interest, e.g., a GSK-derived biotinylated peptide substrate. The phosphopeptide product is quantitated using a Homogenous Time-Resolved Fluorescence (HTRF) assay system (Park et al., 1999, Anal. Biochem. 269:94-104). The reaction mixture contains suitable amounts of ATP, peptide substrate, and the CML progression protein. The peptide substrate has a suitable amino acid sequence and is biotinylated at the N-terminus. The kinase reaction is incubated, and then terminated with Stop/Detection Buffer and GSK3α anti-phosphoserine antibody (e.g., Cell Signaling Technologies, Beverly, Mass.; Cat# 9338) labeled with europium-chelate (e.g., from Perkin Elmer, Boston, Mass.). The reaction is allowed to equilibrate, and relative fluorescent units are determined. Inhibitor compounds are assayed in the reaction described above, to determine compound IC50s. A particular compound is added to in a half-log dilution series covering a suitable range of concentrations, e.g., from 1 nM to 100 μM. Relative phospho substrate formation, read as HTRF fluorescence units, is measured over the range of compound concentrations and a titration curve generated using a four parameter sigmoidal fit. Specific compounds having IC₅₀ below a predetermined threshold value, e.g., ≦50 μM against a substrate, can be identified.

The extent of peptide phosphorylation can be determined by Homogeneous Time Resolved Fluorescence (HTRF) using a lanthanide chelate (Lance)-coupled monoclonal antibody specific for the phosphopeptide in combination with a streptavidin-linked allophycocyanin (SA-APC) fluorophore which binds to the biotin moiety on the peptide. When the Lance and APC are in proximity (i.e. bound to the same phosphopeptide molecule), a non-radiative energy transfer takes place from the Lance to the APC, followed by emission of light from APC at 665 nm. The assay can be run using various assay format, e.g., streptavidin flash plate assay, streptavidin filter plate assay.

A standard PKA assay can be used to assay the activity of protein kinase A (PKA). A standard PKC assay can be used to assay the activity of protein kinase C (PKC). The most common methods for assaying PKA or PKC activity involves measuring the transfer of ³²P-labeled phosphate to a protein or peptide substrate that can be captured on phosphocellulose filters via weak electrostatic interactions.

Kinase inhibitors can be identified using fluorescence polarization to monitor kinase activity. This assay utilizes GST-CML progression protein, peptide substrate, peptide substrate tracer, an anti-phospho monoclonal IgG, and the inhibitor compound. Reactions are incubated for a period of time and then terminated. Stopped reactions are incubated and fluorescence polarization values determined.

In a specific embodiment, a standard SPA Filtration Assay and FlashPlate® Kinase Assay can be used to measure the activity of a CML progression protein. In these assays, GST-CML progression protein, biotinylated peptide substrate, ATP, and ³³P-γ-ATP are allowed to react. After a suitable period of incubation, the reactions are terminated. In a SPA Filtration Assay, peptide substrate is allowed to bind Scintilation proximity assay (SPA) beads (Amersham Biosciences), followed by filtration on a Packard GF/B Unifilter plate and washed with phosphate buffered saline. Dried plates are sealed and the amount of ³³P incorporated into the peptide substrate is determined. In a FlashPlate® Kinase Assay, a suitable amount of the reaction is transferred to streptavidin-coated FlashPlates® (NEN) and incubated. Plates are washed, dried, sealed and the amount of ³³P incorporated into the peptide substrate is determined.

A standard DELFIA® Kinase Assay can also be used. In a DELFIA® Kinase Assay, GST-CML progression protein, peptide substrate, and ATP are allowed to react. After the reactions are terminated, the biotin-peptide substrates are captured in the stopped reactions. Wells are washed and reacted with anti-phospho polyclonal antibody and europium labeled anti-rabbit-IgG. Wells are washed and europium released from the bound antibody is detected.

Other assays, such as those described in WO 04/080973, WO 02/070494, and WO 03/101444, may also be utilized to determine biological activity of the instant compounds.

5.5.2. Screening Compounds that Modulate Expression or Activity of a Gene and/or its Products

For CML progression genes that are kinases, inhibitor compounds can be assayed for their ability to inhibit a CML progression protein in hematopoetic stem cells and/or immature myeloid cells by monitoring the phosphorylation or autophosphorylation in response to the compound. Cells are grown in culture medium. Cells are pooled, counted, seeded into 6 well dishes at 200,000 cells per well in 2 ml media, and incubated. Serial dilution series of compounds or control are added to each well and incubated. Following the incubation period, each well is washed and Protease Inhibitor Cocktail Complete is added to each well. Lysates are then transferred to microcentrifuge tubes and frozen at −80° C. Lysates are thawed on ice and cleared by centrifugation and the supernatants are transferred to clean tubes. Samples are electorphoresed and proteins are transferred onto PVDF. Blots are then blocked and probed using an antibody against phospho-serine or phospho threonine. Bound antibody is visualized using a horseradish peroxidase conjugated secondary antibody and enhanced chemiluminescence. After stripping of the first antibody set, blots are re-probed for total CML progression protein, using a monoclonal antibody specific for the CML progression protein. The CML progression protein monoclonal is detected using a sheep anti-mouse IgG coupled to horseradish peroxidase and enhanced chemiluminescence. ECL exposed films are scanned and the intensity of specific bands is quantitated. Titrations are evaluated for level of phosphor-Ser signal normalized to total CML progression protein and IC50 values are calculated.

Detection of phosphonucleolin in cell lysates can be carried out using biotinylated anti-nucleolin antibody and ruthenylated goat anti-mouse antibody. To each well of a 96-well plate is added biotynylated anti-nucleolin antibody and streptavidin coated paramagnetic beads, along with a suitable cell lysate. The antibodies and lysate are incubated. Next, another anti-phosphonucleolin antibody are added to each well of the lysate mix and incubated. Lastly, the ruthenylated goat anti-mouse antibody in antibody buffer is added to each well and incubated. The lysate antibody mixtures are read and EC50s for compound dependent increases in phosphor-nucleolin are determined.

The compounds identified in the screen include compounds that demonstrate the ability to selectively modulate the expression or activity of a CML progression gene or its encoded protein. These compounds include but are not limited to siRNA, antisense nucleic acid, ribozyme, triple helix forming nucleic acid, antibody, and polypeptide molecules, aptamrs, and small organic or inorganic molecules.

5.6. Methods of Performing RNA Interference

Any method known in the art for gene silencing can be used in the present invention (see, e.g., Guo et al., 1995, Cell 81:611-620; Fire et al., 1998, Nature 391:806-811; Grant, 1999, Cell 96:303-306; Tabara et al., 1999, Cell 99:123-132; Zamore et al., 2000, Cell 101:25-33; Bass, 2000, Cell 101:235-238; Petcherski et al., 2000, Nature 405:364-368; Elbashir et al., Nature 411:494-498; Paddison et al., Proc. Natl. Acad. Sci. USA 99:1443-1448). The siRNAs targeting a gene can be designed according to methods known in the art (see, e.g., International Application Publication No. WO 2005/018534, published on Mar. 3, 2005, and Elbashir et al., 2002, Methods 26:199-213, each of which is incorporated herein by reference in its entirety).

An siRNA having only partial sequence homology to a target gene can also be used (see, e.g., International Application Publication No. WO 2005/018534, published on Mar. 3, 2005, which is incorporated herein by reference in its entirety). In one embodiment, an siRNA that comprises a sense strand contiguous nucleotide sequence of 11-18 nucleotides that is identical to a sequence of a transcript of a gene but the siRNA does not have full length homology to any sequences in the transcript is used to silence the gene. Preferably, the contiguous nucleotide sequence is in the central region of the siRNA molecules. A contiguous nucleotide sequence in the central region of an siRNA can be any continuous stretch of nucleotide sequence in the siRNA which does not begin at the 3′ end. For example, a contiguous nucleotide sequence of 11 nucleotides can be the nucleotide sequence 2-12, 3-13, 4-14, 5-15, 6-16, 7-17, 8-18, or 9-19. In preferred embodiments, the contiguous nucleotide sequence is 11-16, 11-15, 14-15, 11, 12, or 13 nucleotides in length.

In another embodiment, an siRNA that comprises a 3′ sense strand contiguous nucleotide sequence of 9-18 nucleotides which is identical to a sequence of a transcript of a gene but which siRNA does not have full length sequence identity to any contiguous sequences in the transcript is used to silence the gene. In this application, a 3′ 9-18 nucleotide sequence is a continuous stretch of nucleotides that begins at the first paired base, i.e., it does not comprise the two base 3′ overhang. Thus, when it is stated that a particular nucleotide sequence is at the 3′ end of the siRNA, the 2 base overhang is not considered. In preferred embodiments, the contiguous nucleotide sequence is 9-16, 9-15, 9-12, 11, 10, or 9 nucleotides in length.

An siRNA having only partial sequence homology to its target genes is especially useful for silencing a plurality of different genes in a cell. In one embodiment, an siRNA is used to silence a plurality of different genes, the transcript of each of the genes comprises a nucleotide sequence that is identical to a central contiguous nucleotide sequence of at least 11 nucleotides of the sense strand or the antisense strand of the siRNA, and/or comprises a nucleotide sequence that is identical to a contiguous nucleotide sequence of at least 9 nucleotides at the 3′ end of the sense strand or the antisense strand of the siRNA. In preferred embodiments, the central contiguous nucleotide sequence is 11-15, 14-15, 11, 12, or 13 nucleotides in length. In other preferred embodiments, the 3′ contiguous nucleotide sequence is 9-15, 9-12, 11, 10, or 9 nucleotides in length.

In one embodiment, in vitro siRNA transfection is carried out as follows: one day prior to transfection, 100 microliters of chosen cells, e.g., cervical cancer HeLa cells (ATCC, Cat. No. CCL-2), grown in DMEM/10% fetal bovine serum (Invitrogen, Carlsbad, Calif.) to approximately 90% confluency are seeded in a 96-well tissue culture plate (Corning, Corning, N.Y.) at 1500 cells/well. For each transfection 85 microliters of OptiMEM (Invitrogen) is mixed with 5 microliter of serially diluted siRNA (Dharna on, Denver) from a 20 micro molar stock. For each transfection 5 microliter OptiMEM is mixed with 5 microliter Oligofectamine reagent (Invitrogen) and incubated 5 minutes at room temperature. The 10 microliter OptiMEM/Oligofectamine mixture is dispensed into each tube with the OptiMEM/siRNA mixture, mixed and incubated 15-20 minutes at room temperature. 10 microliter of the transfection mixture is aliquoted into each well of the 96-well plate and incubated for 4 hours at 37° C. and 5% CO₂.

In preferred embodiments, an siRNA pool containing at least k (k=2, 3, 4, 5, 6 or 10) different siRNAs targeting the secondary target gene at different sequence regions is used to transfect the cells. In another preferred embodiment, an siRNA pool containing at least k (k=2, 3, 4, 5, 6 or 10) different siRNAs targeting two or more different target genes is used to transfect the cells.

In a preferred embodiment, the total siRNA concentration of the pool is about the same as the concentration of a single siRNA when used individually, e.g., 100 nM. Preferably, the total concentration of the pool of siRNAs is an optimal concentration for silencing the intended target gene. An optimal concentration is a concentration further increase of which does not increase the level of silencing substantially. In one embodiment, the optimal concentration is a concentration further increase of which does not increase the level of silencing by more than 5%, 10% or 20%. In a preferred embodiment, the composition of the pool, including the number of different siRNAs in the pool and the concentration of each different siRNA, is chosen such that the pool of siRNAs causes less than 30%, 20%, 10% or 5%, 1%, 0.1% or 0.01% of silencing of any off-target genes (e.g., as determined by standard nucleic acid assay, e.g., PCR). In another preferred embodiment, the concentration of each different siRNA in the pool of different siRNAs is about the same. In still another preferred embodiment, the respective concentrations of different siRNAs in the pool are different from each other by less than 5%, 10%, 20% or 50% of the concentration of any one siRNA or said total siRNA concentration of said different siRNAs. In still another preferred embodiment, at least one siRNA in the pool of different siRNAs constitutes more than 90%, 80%, 70%, 50%, or 20% of the total siRNA concentration in the pool. In still another preferred embodiment, none of the siRNAs in the pool of different siRNAs constitutes more than 90%, 80%, 70%, 50%, or 20% of the total siRNA concentration in the pool. In other embodiments, each siRNA in the pool has an concentration that is lower than the optimal concentration when used individually. In a preferred embodiment, each different siRNA in the pool has an concentration that is lower than the concentration of the siRNA that is effective to achieve at least 30%, 50%, 75%, 80%, 85%, 90% or 95% silencing when used in the absence of other siRNAs or in the absence of other siRNAs designed to silence the gene. In another preferred embodiment, each different siRNA in the pool has a concentration that causes less than 30%, 20%, 10% or 5% of silencing of the gene when used in the absence of other siRNAs or in the absence of other siRNAs designed to silence the gene. In a preferred embodiment, each siRNA has a concentration that causes less than 30%, 20%, 10% or 5% of silencing of the target gene when used alone, while the plurality of siRNAs causes at least 80% or 90% of silencing of the target gene.

Another method for gene silencing is to introduce an shRNA, for short hairpin RNA (see, e.g., Paddison et al., 2002, Genes Dev. 16, 948-958; Brummelkamp et al., 2002, Science 296, 550-553; Sui, G. et al. 2002, Proc. Natl. Acad. Sci. USA 99, 5515-5520, all of which are incorporated by reference herein in their entirety), which can be processed in the cells into siRNA. In this method, a desired siRNA sequence is expressed from a plasmid (or virus) as an inverted repeat with an intervening loop sequence to form a hairpin structure. The resulting RNA transcript containing the hairpin is subsequently processed by Dicer to produce siRNAs for silencing. Plasmid-based shRNAs can be expressed stably in cells, allowing long-term gene silencing in cells both in vitro and in vivo, e.g., in animals (see, McCaffrey et al. 2002, Nature 418, 38-39; Xia et al., 2002, Nat. Biotech. 20, 1006-1010; Lewis et al., 2002, Nat. Genetics 32, 107-108; Rubinson et al., 2003, Nat. Genetics 33, 401-406; Tiscornia et al., 2003, Proc. Natl. Acad. Sci. USA 100, 1844-1848, all of which are incorporated by reference herein in their entirety). Thus, in one embodiment, a plasmid-based shRNA is used.

In a preferred embodiment, shRNAs are expressed from recombinant vectors introduced either transiently or stably integrated into the genome (see, e.g., Paddison et al., 2002, Genes Dev 16:948-958; Sui et al., 2002, Proc Natl Acad Sci USA 99:5515-5520; Yu et al., 2002, Proc Natl Acad Sci USA 99:6047-6052; Miyagishi et al., 2002, Nat Biotechnol 20:497-500; Paul et al., 2002, Nat Biotechnol 20:505-508; Kwak et al., 2003, J Pharmacol Sci 93:214-217; Brummelkamp et al., 2002, Science 296:550-553; Boden et al., 2003, Nucleic Acids Res 31:5033-5038; Kawasaki et al., 2003, Nucleic Acids Res 31:700-707). The siRNA that disrupts the target gene can be expressed (via an shRNA) by any suitable vector which encodes the shRNA. The vector can also encode a marker which can be used for selecting clones in which the vector or a sufficient portion thereof is integrated in the host genome such that the shRNA is expressed. Any standard method known in the art can be used to deliver the vector into the cells. In one embodiment, cells expressing the shRNA are generated by transfecting suitable cells with a plasmid containing the vector. Cells can then be selected by the appropriate marker. Clones are then picked, and tested for knockdown. In a preferred embodiment, the expression of the shRNA is under the control of an inducible promoter such that the silencing of its target gene can be turned on when desired. Inducible expression of an siRNA is particularly useful for targeting essential genes.

In one embodiment, the expression of the shRNA is under the control of a regulated promoter that allows tuning of the silencing level of the target gene. This allows screening against cells in which the target gene is partially knocked out. As used herein, a “regulated promoter” refers to a promoter that can be activated when an appropriate inducing agent is present. An “inducing agent” can be any molecule that can be used to activate transcription by activating the regulated promoter. An inducing agent can be, but is not limited to, a peptide or polypeptide, a hormone, or an organic small molecule. An analogue of an inducing agent, i.e., a molecule that activates the regulated promoter as the inducing agent does, can also be used. The level of activity of the regulated promoter induced by different analogues may be different, thus allowing more flexibility in tuning the activity level of the regulated promoter. The regulated promoter in the vector can be any mammalian transcription regulation system known in the art (see, e.g., Gossen et al, 1995, Science 268:1766-1769; Lucas et al, 1992, Annu. Rev. Biochem. 61:1131; Li et al., 1996, Cell 85:319-329; Saez et al., 2000, Proc. Natl. Acad. Sci. USA 97:14512-14517; and Pollock et al., 2000, Proc. Nati. Acad. Sci. USA 97:13221-13226). In preferred embodiments, the regulated promoter is regulated in a dosage and/or analogue dependent manner. In one embodiment, the level of activity of the regulated promoter is tuned to a desired level by a method comprising adjusting the concentration of the inducing agent to which the regulated promoter is responsive. The desired level of activity of the regulated promoter, as obtained by applying a particular concentration of the inducing agent, can be determined based on the desired silencing level of the target gene.

In one embodiment, a tetracycline regulated gene expression system is used (see, e.g., Gossen et al, 1995, Science 268:1766-1769; U.S. Pat. No. 6,004,941). A tet regulated system utilizes components of the tet repressor/operator/inducer system of prokaryotes to regulate gene expression in eukaryotic cells. Thus, the invention provides methods for using the tet regulatory system for regulating the expression of an shRNA linked to one or more tet operator sequences. The methods involve introducing into a cell a vector encoding a fusion protein that activates transcription. The fusion protein comprises a first polypeptide that binds to a tet operator sequence in the presence of tetracycline or a tetracycline analogue operatively linked to a second polypeptide that activates transcription in cells. By modulating the concentration of a tetracycline, or a tetracycline analogue, expression of the tet operator-linked shRNA is regulated.

In other embodiments, an ecdyson regulated gene expression system (see, e.g., Saez et al., 2000, Proc. Natl. Acad. Sci. USA 97:14512-14517), or an MMTV glucocorticoid response element regulated gene expression system (see, e.g., Lucas et al, 1992, Annu. Rev. Biochem. 61:1131) may be used to regulate the expression of the shRNA.

In one embodiment, the pRETRO-SUPER (pRS) vector which encodes a puromycin-resistance marker and drives shRNA expression from an HI (RNA Pol III) promoter is used. The pRS-shRNA plasmid can be generated by any standard method known in the art. In one embodiment, the pRS-shRNA is deconvoluted from the library plasmid pool for a chosen gene by transforming bacteria with the pool and looking for clones containing only the plasmid of interest. Preferably, a 19mer siRNA sequence is used along with suitable forward and reverse primers for sequence specific PCR. Plasmids are identified by sequence specific PCR, and confirmed by sequencing. Cells expressing the shRNA are generated by transfecting suitable cells with the pRS-shRNA plasmid. Cells are selected by the appropriate marker, e.g., puromycin, and maintained until colonies are evident. Clones are then picked, and tested for knockdown. In another embodiment, an shRNA is expressed by a plasmid, e.g., a pRS-shRNA. The knockdown by the pRS-shRNA plasmid, can be achieved by transfecting cells using Lipofectamine 2000 (Invitrogen).

In yet another method, siRNAs can be delivered to an organ or tissue in an animal, such a human, in vivo (see, e.g., Song et al. 2003, Nat. Medicine 9, 347-351; Sorensen et al., 2003, J Mol. Biol. 327, 761-766; Lewis et al., 2002, Nat. Genetics 32, 107-108, all of which are incorporated by reference herein in their entirety). In this method, a solution of siRNA is injected intravenously into the animal. The siRNA can then reach an organ or tissue of interest and effectively reduce the expression of the target gene in the organ or tissue of the animal.

5.7. Production of CML Progression/Target or IM Resistance Proteins and Peptides

CML progression proteins, or peptide fragments thereof, can be prepared for uses according to the present invention. For example, CML progression proteins, or peptide fragments thereof, can be used for the generation of antibodies, in diagnostic assays, for screening of inhibitors, or for the identification of other cellular gene products involved in the regulation of expression and/or activity of a CML progression gene.

The CML progression proteins or peptide fragments thereof, may be produced by recombinant DNA technology using techniques well known in the art. The amino acid sequences of the CML progression proteins are well-known and can be obtained from, e.g., GenBank®. Methods which are well known to those skilled in the art can be used to construct expression vectors containing CML progression protein coding sequences and appropriate transcriptional and translational control signals. These methods include, for example, in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination. See, for example, the techniques described in Sambrook et al., 1989, supra, and Ausubel et al., 1989, supra. Alternatively, RNA capable of encoding CML progression protein sequences may be chemically synthesized using, for example, synthesizers. See, for example, the techniques described in “Oligonucleotide Synthesis”, 1984, Gait, M. J. ed., IRL Press, Oxford, which is incorporated herein by reference in its entirety.

A variety of host-expression vector systems may be utilized to express the CML progression gene coding sequences. Such host-expression systems represent vehicles by which the coding sequences of interest may be produced and subsequently purified, but also represent cells which may, when transformed or transfected with the appropriate nucleotide coding sequences, exhibit the CML progression protein in situ. These include but are not limited to microorganisms such as bacteria (e.g., E. coli, B. subtilis) transformed with recombinant bacteriophage DNA, plasmid DNA or cosmid DNA expression vectors containing CML progression protein coding sequences; yeast (e.g., Saccharomyces, Pichia) transformed with recombinant yeast expression vectors containing the CML progression protein coding sequences; insect cell systems infected with recombinant virus expression vectors (e.g., baculovirus) containing the CML progression protein coding sequences; plant cell systems infected with recombinant virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or transformed with recombinant plasmid expression vectors (e.g., Ti plasmid) containing CML progression protein coding sequences; or mammalian cell systems (e.g., COS, CHO, BHK, 293, 3T3, N2a) harboring recombinant expression constructs containing promoters derived from the genome of mammalian cells (e.g., metallothionein promoter) or from mammalian viruses (e.g., the adenovirus late promoter; the vaccinia virus 7.5K promoter).

In bacterial systems, a number of expression vectors may be advantageously selected depending upon the use intended for the CML progression protein being expressed. For example, when a large quantity of such a protein is to be produced, for the generation of pharmaceutical compositions of CML progression protein protein or for raising antibodies to CML progression protein protein, for example, vectors which direct the expression of high levels of fusion protein products that are readily purified may be desirable. Such vectors include, but are not limited, to the E. coli expression vector pUR278 (Ruther et al., 1983, EMBO J. 2:1791), in which the CML progression protein coding sequence may be ligated individually into the vector in frame with the lac Z coding region so that a fusion protein is produced; pIN vectors (Inouye & Inouye, 1985, Nucleic Acids Res. 13:3101-3109; Van Heeke & Schuster, 1989, J. Biol. Chem. 264:5503-5509); and the like. pGEX vectors may also be used to express foreign polypeptides as fusion proteins with glutathione S-transferase (GST). In general, such fusion proteins are soluble and can easily be purified from lysed cells by adsorption to glutathione-agarose beads followed by elution in the presence of free glutathione. The pGEX vectors are designed to include thrombin or factor Xa protease cleavage sites so that the cloned target gene product can be released from the GST moiety.

In an insect system, Autographa californica nuclear polyhedrosis virus (AcNPV) is used as a vector to express foreign genes. The virus grows in Spodoptera frugiperda cells. The CML progression gene coding sequence may be cloned individually into non-essential regions (for example the polyhedrin gene) of the virus and placed under control of an AcNPV promoter (for example the polyhedrin promoter). Successful insertion of CML progression gene coding sequence will result in inactivation of the polyhedrin gene and production of non-occluded recombinant virus (i.e., virus lacking the proteinaceous coat coded for by the polyhedrin gene). These recombinant viruses are then used to infect Spodoptera frugiperda cells in which the inserted gene is expressed. (E.g., see Smith et al., 1983, J. Virol. 46: 584; Smith, U.S. Pat. No. 4,215,051).

In mammalian host cells, a number of viral-based expression systems may be utilized. In cases where an adenovirus is used as an expression vector, the CML progression gene coding sequence of interest may be ligated to an adenovirus transcription/translation control complex, e.g., the late promoter and tripartite leader sequence. This chimeric gene may then be inserted in the adenovirus genome by in vitro or in vivo recombination. Insertion in a non-essential region of the viral genome (e.g., region E1 or E3) will result in a recombinant virus that is viable and capable of expressing CML progression protein in infected hosts. (E.g., See Logan & Shenk, 1984, Proc. Natl. Acad. Sci. USA 81:3655-3659). Specific initiation signals may also be required for efficient translation of inserted CML progression protein coding sequences. These signals include the ATG initiation codon and adjacent sequences. In cases where an entire CML progression gene, including its own initiation codon and adjacent sequences, is inserted into the appropriate expression vector, no additional translational control signals may be needed. However, in cases where only a portion of the CML progression gene coding sequence is inserted, exogenous translational control signals, including, perhaps, the ATG initiation codon, must be provided. Furthermore, the initiation codon must be in phase with the reading frame of the desired coding sequence to ensure translation of the entire insert. These exogenous translational control signals and initiation codons can be of a variety of origins, both natural and synthetic. The efficiency of expression may be enhanced by the inclusion of appropriate transcription enhancer elements, transcription terminators, etc. (see Bittner et al., 1987, Methods in Enzymol. 153:516-544).

In addition, a host cell strain may be chosen which modulates the expression of the inserted sequences, or modifies and processes the gene product in the specific fashion desired. Such modifications (e.g., glycosylation) and processing (e.g., cleavage) of protein products may be important for the function of the protein. Different host cells have characteristic and specific mechanisms for the post-translational processing and modification of proteins and gene products. Appropriate cell lines or host systems can be chosen to ensure the correct modification and processing of the foreign protein expressed. To this end, eukaryotic host cells which possess the cellular machinery for proper processing of the primary transcript, glycosylation, and phosphorylation of the gene product may be used. Such mammalian host cells include but are not limited to CHO, VERO, BHK, HeLa, COS, MDCK, 293, 3T3, W138.

For long-term, high-yield production of recombinant proteins, stable expression is preferred. For example, cell lines which stably express the CML progression protein may be engineered. Rather than using expression vectors which contain viral origins of replication, host cells can be transformed with DNA controlled by appropriate expression control elements (e.g., promoter, enhancer, sequences, transcription terminators, polyadenylation sites, etc.), and a selectable marker. Following the introduction of the foreign DNA, engineered cells may be allowed to grow for 1-2 days in an enriched media, and then are switched to a selective media. The selectable marker in the recombinant plasmid confers resistance to the selection and allows cells to stably integrate the plasmid into their chromosomes and grow to form foci which in turn can be cloned and expanded into cell lines. This method may advantageously be used to engineer cell lines which express the CML progression protein. Such engineered cell lines may be particularly useful in screening and evaluation of compounds that affect the endogenous activity of the CML progression protein.

In another embodiment, the expression characteristics of an endogenous gene (e.g., a CML progression gene) within a cell, cell line or microorganism may be modified by inserting a DNA regulatory element heterologous to the endogenous gene of interest into the genome of a cell, stable cell line or cloned microorganism such that the inserted regulatory element is operatively linked with the endogenous gene (e.g., a CML progression gene) and controls, modulates, activates, or inhibits the endogenous gene. For example, endogenous CML progression genes which are normally “transcriptionally silent”, i.e., a CML progression gene which is normally not expressed, or is expressed only at very low levels in a cell line or microorganism, may be activated by inserting a regulatory element which is capable of promoting the expression of the gene product in that cell line or microorganism. Alternatively, transcriptionally silent, endogenous CML progression genes may be activated by insertion of a promiscuous regulatory element that works across cell types.

A heterologous regulatory element may be inserted into a stable cell line or cloned microorganism, such that it is operatively linked with and activates or inhibits expression of endogenous CML progression genes, using techniques, such as targeted homologous recombination, which are well known to those of skill in the art, and described e.g., in Chappel, U.S. Pat. No. 5,272,071; PCT Publication No. WO 91/06667 published May 16, 1991; Skoultchi, U.S. Pat. No. 5,981,214; and Treco et al U.S. Pat. No. 5,968,502 and PCT Publication No. WO 94/12650 published Jun. 9, 1994. Alternatively, non-targeted, e.g. non-homologous recombination techniques may be used which are well-known to those of skill in the art and described, e.g., in PCT Publication No. WO 99/15650 published Apr. 1, 1999.

CML progression gene activation (or inactivation) may also be accomplished using designer transcription factors using techniques well known in the art. Briefly, a designer zinc finger protein transcription factor (ZFP-TF) is made which is specific for a regulatory region of the CML progression gene to be activated or inactivated. A construct encoding this designer ZFP-TF is then provided to a host cell in which the CML progression gene is to be controlled. The construct directs the expression of the designer ZFP-TF protein, which in turn specifically modulates the expression of the endogenous CML progression gene. The following references relate to various aspects of this approach in further detail: Wang & Pabo, 1999, Proc. Natl. Acad. Sci. USA 96, 9568; Berg, 1997, Nature Biotechnol. 15, 323; Greisman & Pabo, 1997, Science 275, 657; Berg & Shi, 1996, Science 271, 1081; Rebar & Pabo, 1994, Science 263, 671; Rhodes & Klug, 1993, Scientific American 269, 56; Pavletich & Pabo, 1991, Science 252, 809; Liu et al., 2001, J. Biol. Chem. 276, 11323; Zhang et al., 2000, J. Biol. Chem. 275, 33850; Beerli et al., 2000, Proc. Natl. Acad. Sci. USA 97, 1495; Kang et al., 2000, J. Biol. Chem. 275, 8742; Beerli et al., 1998, Proc. Natl. Acad. Sci. USA 95, 14628; Kim & Pabo, 1998, Proc. Natl. Acad. Sci. USA 95, 2812; Choo et al., 1997, J. Mol. Biol. 273, 525; Kim & Pabo, 1997, J. Biol. Chem. 272, 29795; Liu et al, 1997, Proc. Natl. Acad. Sci. USA 94, 5525; Kim et al, 1997, Proc. Natl. Acad. Sci. USA 94, 3616; Kikyo et al., 2000, Science 289, 2360; Robertson & Wolffe, 2000, Nature Reviews 1, 11; and Gregory, 2001, Curr. Opin. Genet. Devt. 11, 142.

A number of selection systems may be used, including but not limited to the herpes simplex virus thymidine kinase (Wigler, et al., 1977, Cell 11:223), hypoxanthine-guanine phosphoribosyltransferase (Szybalska & Szybalski, 1962, Proc. Natl. Acad. Sci. USA 48:2026), and adenine phosphoribosyltransferase (Lowy, et al., 1980, Cell 22:817) genes can be employed in tk⁻, hgprt⁻ or aprt⁻ cells, respectively. Also, antimetabolite resistance can be used as the basis of selection for the following genes: dhfr, which confers resistance to methotrexate (Wigler, et al., 1980, Natl. Acad. Sci. USA 77:3567; O'Hare, et al., 1981, Proc. Natl. Acad. Sci. USA 78:1527); gpt, which confers resistance to mycophenolic acid (Mulligan & Berg, 1981, Proc. Natl. Acad. Sci. USA 78:2072); neo, which confers resistance to the aminoglycoside G-418 (Colberre-Garapin, et al., 1981, J. Mol. Biol. 150:1); and hygro, which confers resistance to hygromycin (Santerre, et al., 1984, Gene 30:147).

Alternatively, any fusion protein may be readily purified by utilizing an antibody specific for the fusion protein being expressed. For example, a system described by Janknecht et al. allows for the ready purification of non-denatured fusion proteins expressed in human cell lines (Janknecht, et al., 1991, Proc. Natl. Acad. Sci. USA 88: 8972-8976). In this system, the gene of interest is subcloned into a vaccinia recombination plasmid such that the gene's open reading frame is translationally fused to an amino-terminal tag consisting of six histidine residues. Extracts from cells infected with recombinant vaccinia virus are loaded onto Ni²⁺.nitriloacetic acid-agarose columns and histidine-tagged proteins are selectively eluted with imidazole-containing buffers.

In a specific embodiment, recombinant human CML progression proteins can be expressed as a fusion protein with glutathione S-transferase at the amino-terminus (GST-CML progression protein) using standard baculovirus vectors and a (Bac-to-Bac®) insect cell expression system purchased from GIBCO™ Invitrogen. Recombinant protein expressed in insect cells can be purified using glutathione sepharose (Amersham Biotech) using standard procedures described by the manufacturer.

5.8. Production of Antibodies that Bind a CML Progression/Target or IM Resistance Protein

CML progression protein or a fragment thereof can be used to raise antibodies which bind CML progression protein. Such antibodies include but are not limited to polyclonal, monoclonal, chimeric, single chain, Fab fragments, and an Fab expression library. In a preferred embodiment, anti CML progression protein C-terminal antibodies are raised using an appropriate C-terminal fragment of a CML progression protein, e.g., the kinase domain. Such antibodies bind the kinase domain of the CML progression protein. In another preferred embodiment, anti CML progression protein N-terminal antibodies are raised using an appropriate N-terminal fragment of a CML progression protein. The N-terminal domain of a CML progression protein are less homologous to other kinases, and therefore offered a more specific target for a particular CML progression protein.

5.8.1. Production of Monoclonal Antibodies Specific for a CML Progression/Target of IM Resistance Protein

Antibodies can be prepared by immunizing a suitable subject with a CML progression protein or a fragment thereof as an immunogen. The antibody titer in the immunized subject can be monitored over time by standard techniques, such as with an enzyme linked immunosorbent assay (ELISA) using immobilized polypeptide. If desired, the antibody molecules can be isolated from the mammal (e.g., from the blood) and further purified by well-known techniques, such as protein A chromatography to obtain the IgG fraction.

At an appropriate time after immunization, e.g., when the specific antibody titers are highest, antibody-producing cells can be obtained from the subject and used to prepare monoclonal antibodies by standard techniques, such as the hybridoma technique originally described by Kohler and Milstein (1975, Nature 256:495-497), the human B cell hybridoma technique by Kozbor et al. (1983, Immunol. Today 4:72), the EBV-hybridoma technique by Cole et al. (1985, Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pp. 77-96) or trioma techniques. The technology for producing hybridomas is well known (see Current Protocols in Immunology, 1994, John Wiley & Sons, Inc., New York, N.Y.). Hybridoma cells producing a monoclonal antibody are detected by screening the hybridoma culture supernatants for antibodies that bind the polypeptide of interest, e.g., using a standard ELISA assay.

Monoclonal antibodies are obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. Thus, the modifier “monoclonal” indicates the character of the antibody as not being a mixture of discrete antibodies. For example, the monoclonal antibodies may be made using the hybridoma method first described by Kohler et al., 1975, Nature, 256:495, or may be made by recombinant DNA methods (U.S. Pat. No. 4,816,567). The term “monoclonal antibody” as used herein also indicates that the antibody is an immunoglobulin.

In the hybridoma method of generating monoclonal antibodies, a mouse or other appropriate host animal, such as a hamster, is immunized as hereinabove described to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the protein used for immunization (see, e.g., U.S. Pat. No. 5,914,112, which is incorporated herein by reference in its entirety).

Alternatively, lymphocytes may be immunized in vitro. Lymphocytes then are fused with myeloma cells using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (Goding, Monoclonal Antibodies: Principles and Practice, pp. 59-103 (Academic Press, 1986)). The hybridoma cells thus prepared are seeded and grown in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, parental myeloma cells. For example, if the parental myeloma cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine (HAT medium), which substances prevent the growth of HGPRT-deficient cells.

Preferred myeloma cells are those that fuse efficiently, support stable high-level production of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. Among these, preferred myeloma cell lines are murine myeloma lines, such as those derived from MOPC-21 and MPC-11 mouse tumors available from the Salk Institute Cell Distribution Center, San Diego, Calif. USA, and SP-2 cells available from the American Type Culture Collection, Rockville, Md. USA.

Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies (Kozbor, 1984, J. Immunol., 133:3001; Brodeur et al., Monoclonal Antibody Production Techniques and Applications, pp. 51-63 (Marcel Dekker, Inc., New York, 1987)). Culture medium in which hybridoma cells are growing is assayed for production of monoclonal antibodies directed against the antigen. Preferably, the binding specificity of monoclonal antibodies produced by hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immuno-absorbent assay (ELISA). The binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson et al., 1980, Anal. Biochem., 107:220.

After hybridoma cells are identified that produce antibodies of the desired specificity, affinity, and/or activity, the clones may be subcloned by limiting dilution procedures and grown by standard methods (Goding, Monoclonal Antibodies: Principles and Practice, pp. 59-103, Academic Press, 1986). Suitable culture media for this purpose include, for example, D-MEM or RPMI-1640 medium. In addition, the hybridoma cells may be grown in vivo as ascites tumors in an animal. The monoclonal antibodies secreted by the subclones are suitably separated from the culture medium, ascites fluid, or serum by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.

Alternative to preparing monoclonal antibody-secreting hybridomas, a monoclonal antibody directed against a CML progression protein or a fragment thereof can be identified and isolated by screening a recombinant combinatorial immunoglobulin library (e.g., an antibody phage display library) with the CML progression protein or the fragment. Kits for generating and screening phage display libraries are commercially available (e.g., Pharmacia Recombinant Phage Antibody System, Catalog No. 27-9400-01; and the Stratagene antigen SurfZAP™ Phage Display Kit, Catalog No. 240612). Additionally, examples of methods and reagents particularly amenable for use in generating and screening antibody display library can be found in, for example, U.S. Pat. Nos. 5,223,409 and 5,514,548; PCT Publication No. WO 92/18619; PCT Publication No. WO 91/17271; PCT Publication No. WO 92/20791; PCT Publication No. WO 92/15679; PCT Publication No. WO 93/01288; PCT Publication No. WO 92/01047; PCT Publication No. WO 92/09690; PCT Publication No. WO 90/02809; Fuchs et al., 1991, Bio/Technology 9:1370-1372; Hay et al., 1992, Hum. Antibod. Hybridomas 3:81-85; Huse et al., 1989, Science 246:1275-1281; Griffiths et al., 1993, EMBO J. 12:725-734.

In addition, techniques developed for the production of “chimeric antibodies” (Morrison, et al., 1984, Proc. Natl. Acad. Sci., 81, 6851-6855; Neuberger, et al., 1984, Nature 312, 604-608; Takeda, et al., 1985, Nature, 314, 452-454) by splicing the genes from a mouse antibody molecule of appropriate antigen specificity together with genes from a human antibody molecule of appropriate biological activity can be used. A chimeric antibody is a molecule in which different portions are derived from different animal species, such as those having a variable region derived from a murine mAb and a human immunoglobulin constant region. (See, e.g., Cabilly et al., U.S. Pat. No. 4,816,567; and Boss et al., U.S. Pat. No. 4,816,397, which are incorporated herein by reference in their entirety.)

Humanized antibodies are antibody molecules from non-human species having one or more complementarity determining regions (CDRs) from the non-human species and a framework region from a human immunoglobulin molecule. (see e.g., U.S. Pat. No. 5,585,089, which is incorporated herein by reference in its entirety.) Such chimeric and humanized monoclonal antibodies can be produced by recombinant DNA techniques known in the art, for example using methods described in PCT Publication No. WO 87/02671; European Patent Application 184,187; European Patent Application 171,496; European Patent Application 173,494; PCT Publication No. WO 86/01533; U.S. Pat. Nos. 4,816,567 and 5,225,539; European Patent Application 125,023; Better et al., 1988, Science 240:1041-1043; Liu et al., 1987, Proc. Natl. Acad. Sci. USA 84:3439-3443; Liu et al., 1987, J. Immunol. 139:3521-3526; Sun et al., 1987, Proc. Natl. Acad. Sci. USA 84:214-218; Nishimura et al., 1987, Canc. Res. 47:999-1005; Wood et al., 1985, Nature 314:446-449; Shaw et al., 1988, J. Natl. Cancer Inst. 80:1553-1559; Morrison 1985, Science 229:1202-1207; Oi et al., 1986, Bio/Techniques 4:214; Jones et al., 1986, Nature 321:552-525; Verhoeyan et al., 1988, Science 239:1534; and Beidler et al., 1988, J. Immunol. 141:4053-4060.

Complementarity determining region (CDR) grafting is another method of humanizing antibodies. It involves reshaping murine antibodies in order to transfer full antigen specificity and binding affinity to a human framework (Winter et al. U.S. Pat. No. 5,225,539). CDR-grafted antibodies have been successfully constructed against various antigens, for example, antibodies against IL-2 receptor as described in Queen et al., 1989 (Proc. Natl. Acad. Sci. USA 86:10029); antibodies against cell surface receptors-CAMPATH as described in Riechmann et al. (1988, Nature, 332:323; antibodies against hepatitis B in Cole et al. (1991, Proc. Natl. Acad. Sci. USA 88:2869); as well as against viral antigens-respiratory syncitial virus in Tempest et al. (1991, Bio-Technology 9:267). CDR-grafted antibodies are generated in which the CDRs of the murine monoclonal antibody are grafted into a human antibody. Following grafting, most antibodies benefit from additional amino acid changes in the framework region to maintain affinity, presumably because framework residues are necessary to maintain CDR conformation, and some framework residues have been demonstrated to be part of the antigen binding site. However, in order to preserve the framework region so as not to introduce any antigenic site, the sequence is compared with established germline sequences followed by computer modeling.

Completely human antibodies are particularly desirable for therapeutic treatment of human patients. Such antibodies can be produced using transgenic mice which are incapable of expressing endogenous immunoglobulin heavy and light chain genes, but which can express human heavy and light chain genes. The transgenic mice are immunized in the normal fashion with a CML progression protein.

Monoclonal antibodies directed against a CML progression protein can be obtained using conventional hybridoma technology. The human immunoglobulin transgenes harbored by the transgenic mice rearrange during B cell differentiation, and subsequently undergo class switching and somatic mutation. Thus, using such a technique, it is possible to produce therapeutically useful IgG, IgA and IgE antibodies. For an overview of this technology for producing human antibodies, see Lonberg and Huszar (1995, Int. Rev. Immunol. 13:65-93). For a detailed discussion of this technology for producing human antibodies and human monoclonal antibodies and protocols for producing such antibodies, see e.g., U.S. Pat. No. 5,625,126; U.S. Pat. No. 5,633,425; U.S. Pat. No. 5,569,825; U.S. Pat. No. 5,661,016; and U.S. Pat. No. 5,545,806. In addition, companies such as Abgenix, Inc. (Freemont, Calif., see, for example, U.S. Pat. No. 5,985,615) and Medarex, Inc. (Princeton, N.J.), can be engaged to provide human antibodies directed against a CML progression protein or a fragment thtereof using technology similar to that described above.

Completely human antibodies which recognize and bind a selected epitope can be generated using a technique referred to as “guided selection.” In this approach a selected non-human monoclonal antibody, e.g., a mouse antibody, is used to guide the selection of a completely human antibody recognizing the same epitope (Jespers et al., 1994, Bio/technology 12:899-903).

A pre-existing anti-CML progression protein antibody can be used to isolate additional antigens of the CML progression protein by standard techniques, such as affinity chromatography or immunoprecipitation for use as immunogens. Moreover, such an antibody can be used to detect the protein (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of CML progression protein. Detection can be facilitated by coupling the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, beta-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include 125I, 131I, 35S or 3H.

5.8.2. Production of Polyclonal anti-CML Progression/Target or IM Resistance Protein Antibodies

The anti-CML progression protein antibodies can be produced by immunization of a suitable animal, such as but are not limited to mouse, rabbit, and horse.

An immunogenic preparation comprising a CML progression protein or a fragment thereof can be used to prepare antibodies by immunizing a suitable subject (e.g., rabbit, goat, mouse or other mammal). An appropriate immunogenic preparation can contain, for example, recombinantly expressed or chemically synthesized CML progression protein peptide or polypeptide. The preparation can further include an adjuvant, such as Freund's complete or incomplete adjuvant, or similar immunostimulatory agent.

A fragment of a CML progression protein suitable for use as an immunogen comprises at least a portion of the CML progression protein that is 8 amino acids, more preferably 10 amino acids and more preferably still, 15 amino acids long.

The invention also provides chimeric or fusion CML progression protein polypeptides for use as immunogens. As used herein, a “chimeric” or “fusion” CML progression protein polypeptide comprises all or part of a CML progression protein polypeptide operably linked to a heterologous polypeptide. Within the fusion CML progression protein polypeptide, the term “operably linked” is intended to indicate that the CML progression protein polypeptide and the heterologous polypeptide are fused in-frame to each other. The heterologous polypeptide can be fused to the N-terminus or C-terminus of the CML progression protein polypeptide.

One useful fusion CML progression protein polypeptide is a GST fusion CML progression protein polypeptide in which the CML progression protein polypeptide is fused to the C-terminus of GST sequences. Such fusion CML progression protein polypeptides can facilitate the purification of a recombinant CML progression protein polypeptide.

In another embodiment, the fusion CML progression protein polypeptide contains a heterologous signal sequence at its N-terminus so that the CML progression protein polypeptide can be secreted and purified to high homogeneity in order to produce high affinity antibodies. For example, the native signal sequence of an immunogen can be removed and replaced with a signal sequence from another protein. For example, the gp67 secretory sequence of the baculovirus envelope protein can be used as a heterologous signal sequence (Current Protocols in Molecular Biology, Ausubel et al., eds., John Wiley & Sons, 1992). Other examples of eukaryotic heterologous signal sequences include the secretory sequences of melittin and human placental alkaline phosphatase (Stratagene; La Jolla, Calif.). In yet another example, useful prokaryotic heterologous signal sequences include the phoA secretory signal and the protein A secretory signal (Pharmacia Biotech; Piscataway, N.J.).

In yet another embodiment, the fusion CML progression protein polypeptide is an immunoglobulin fusion protein in which all or part of a CML progression protein polypetide is fused to sequences derived from a member of the immunoglobulin protein family. The immunoglobulin fusion proteins can be used as immunogens to produce antibodies directed against the CML progression protein polypetide in a subject.

Chimeric and fusion CML progression protein polypeptide can be produced by standard recombinant DNA techniques. In one embodiment, the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers. Alternatively, PCR amplification of gene fragments can be carried out using anchor primers which give rise to complementary overhangs between two consecutive gene fragments which can subsequently be annealed and reamplified to generate a chimeric gene sequence (e.g., Ausubel et al., supra). Moreover, many expression vectors are commercially available that already encode a fusion domain (e.g., a GST polypeptide). A nucleic acid encoding an immunogen can be cloned into such an expression vector such that the fusion domain is linked in-frame to the polypeptide.

The CML progression protein immunogenic preparation is then used to immunize a suitable animal. Preferably, the animal is a specialized transgenic animal that can secret human antibody. Non-limiting examples include transgenic mouse strains which can be used to produce a polyclonal population of antibodies directed to a specific pathogen (Fishwild et al., 1996, Nature Biotechnology 14:845-851; Mendez et al., 1997, Nature Genetics 15:146-156). In one embodiment of the invention, transgenic mice that harbor the unrearranged human immunoglobulin genes are immunized with the target immunogens. After a vigorous immune response against the immunogenic preparation has been elicited in the mice, the blood of the mice are collected and a purified preparation of human IgG molecules can be produced from the plasma or serum. Any method known in the art can be used to obtain the purified preparation of human IgG molecules, including but is not limited to affinity column chromatography using anti-human IgG antibodies bound to a suitable column matrix. Anti-human IgG antibodies can be obtained from any sources known in the art, e.g., from commercial sources such as Dako Corporation and ICN. The preparation of IgG molecules produced comprises a polyclonal population of IgG molecules that bind to the immunogen or immunogens at different degree of affinity. Preferably, a substantial fraction of the preparation contains IgG molecules specific to the immunogen or immunogens. Although polyclonal preparations of IgG molecules are described, it is understood that polyclonal preparations comprising any one type or any combination of different types of immunoglobulin molecules are also envisioned and are intended to be within the scope of the present invention.

A population of antibodies directed to a CML progression protein can be produced from a phage display library. Polyclonal antibodies can be obtained by affinity screening of a phage display library having a sufficiently large and diverse population of specificities with a CML progression protein or a fragment thereof. Examples of methods and reagents particularly amenable for use in generating and screening antibody display library can be found in, for example, U.S. Pat. Nos. 5,223,409 and 5,514,548; PCT Publication No. WO 92/18619; PCT Publication No. WO 91/17271; PCT Publication No. WO 92/20791; PCT Publication No. WO 92/15679; PCT Publication No. WO 93/01288; PCT Publication No. WO 92/01047; PCT Publication No. WO 92/09690; PCT Publication No. WO 90/02809; Fuchs et al., 1991, Bio/Technology 9:1370-1372; Hay et al., 1992, Hum. Antibod. Hybridomas 3:81-85; Huse et al., 1989, Science 246:1275-1281; Griffiths et al., 1993, EMBO J. 12:725-734. A phage display library permits selection of desired antibody or antibodies from a very large population of specificities. An additional advantage of a phage display library is that the nucleic acids encoding the selected antibodies can be obtained conveniently, thereby facilitating subsequent construction of expression vectors.

In other preferred embodiments, the population of antibodies directed to a CML progression protein or a fragment thereof is produced by a method using the whole collection of selected displayed antibodies without clonal isolation of individual members as described in U.S. Pat. No. 6,057,098, which is incorporated by reference herein in its entirety. Polyclonal antibodies are obtained by affinity screening of a phage display library having a sufficiently large repertoire of specificities with, e.g., an antigenic molecule having multiple epitopes, preferably after enrichment of displayed library members that display multiple antibodies. The nucleic acids encoding the selected display antibodies are excised and amplified using suitable PCR primers. The nucleic acids can be purified by gel electrophoresis such that the full length nucleic acids are isolated. Each of the nucleic acids is then inserted into a suitable expression vector such that a population of expression vectors having different inserts is obtained. The population of expression vectors is then expressed in a suitable host.

5.8.3 Production of Antibody-Drug Conjugates Targeting a CML Progression/Target of IM Resistance Protein

Cancer cells can be targeted and killed using anti-CML progression protein antibody-drug conjugates that target an advanced phase CML hematopoetic stem cell and/or immature myeloid cell expressing a CML progression protein on its surface, e.g., PRAME. For example, an antibody specific for a CML progression protein may be conjugated to a therapeutic moiety such as a cytotoxin, e.g., a cytostatic or cytocidal agent, or a radioactive metal ion. Antibody-drug conjugates can be prepared by method known in the art (see, e.g., Immunoconjugates, Vogel, ed. 1987; Targeted Drugs, Goldberg, ed. 1983; Antibody Mediated Delivery Systems, Rodwell, ed. 1988). Therapeutic drugs, such as but are not limited to, paclitaxol, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicin, doxorubicin, daunorubicin, dihydroxy anthracin dione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, and puromycin and analogs or homologs thereof, can be conjugated to anti-CML progression protein antibodies. Other therapeutic agents that can be conjugated to anti-CML progression protein antibodies include, but are not limited to, antimetabolites, e.g., methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-fluorouracil decarbazine; alkylating agents, e.g., mechlorethamine, thioepa chlorambucil, melphalan, carmustine (BSNU) and lomustine (CCNU), cyclothosphamide, busulfan, dibromomannitol, streptozotocin, mitomycin C, and cis-dichlorodiamine platinum (II) (DDP) cisplatin; anthracyclines, e.g., daunorubicin (daunomycin) and doxorubicin; antibiotics, e.g., dactinomycin (actinomycin), bleomycin, mithramycin, anthramycin (AMC); and anti-mitotic agents, e.g., vincristine and vinblastine. The therapeutic agents that can be conjugated to anti-CML progression protein antibodies may also be a protein or polypeptide possessing a desired biological activity. Other chemotherapeutic agents known in the art, such as those described in Section 5.8.5, infra, can also be conjugated with such an anti-CML progression protein antibody. Such proteins may include, for example, a toxin such as abrin, ricin A, pseudomonas exotoxin, or diphtheria toxin.

The drug molecules can be linked to the anti-CML progression protein antibody via a linker. Any suitable linker can be used for the preparation of such conjugates. In some embodiments, the linker can be a linker that allows the drug molecules to be released from the conjugates in unmodified form at the target site.

The antibodies can also be used diagnostically to, for example, monitor the presence of cancer cells as part of a clinical testing procedure to, e.g., determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, radioactive materials, positron emitting metals using various positron emission tomographies, and nonradioactive paramagnetic metal ions. See generally U.S. Pat. No. 4,741,900 for metal ions which can be conjugated to antibodies for use as diagnostics according to the present invention. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, beta-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include fluorescent proteins, e.g., green fluorescent protein (GFP), umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include ¹²⁵I, ¹³¹I, ¹¹¹In, ¹⁷⁷Lu, ⁹⁰Y or ⁹⁹Tc.

Techniques for conjugating therapeutic moieties to antibodies are well known, see, e.g., Arnon et al., “Monoclonal Antibodies For Immunotargeting Of Drugs In Cancer Therapy”, in Monoclonal Antibodies And Cancer Therapy, Reisfeld et al. (eds.), pp. 243-56 (Alan R. Liss, Inc. 1985); Hellstrom et al., “Antibodies For Drug Delivery”, in Controlled Drug Delivery (2nd Ed.), Robinson et al. (eds.), pp. 623-53 (Marcel Dekker, Inc. 1987); Thorpe, “Antibody Carriers Of Cytotoxic Agents In Cancer Therapy: A Review”, in Monoclonal Antibodies '84: Biological And Clinical Applications, Pinchera et al. (eds.), pp. 475-506 (1985); “Analysis, Results, And Future Prospective Of The Therapeutic Use Of Radiolabeled Antibody In Cancer Therapy”, in Monoclonal Antibodies For Cancer Detection And Therapy, Baldwin et al. (eds.), pp. 303-16 (Academic Press 1985), and Thorpe et al., “The Preparation And Cytotoxic Properties Of Antibody-Toxin Conjugates”, Immunol. Rev., 62:119-58 (1982); each of which is incorporated herein by reference.

Alternatively, an antibody can be conjugated to a second antibody to form an antibody heteroconjugate as described by Segal in U.S. Pat. No. 4,676,980, which is incorporated herein by reference.

5.8.4 Production of Peptides

A CML progression protein-binding peptide or polypeptide or peptide or polypeptide of a CML progression protein may be produced by recombinant DNA technology using techniques well known in the art. Thus; the polypeptide or peptide can be produced by expressing nucleic acid containing sequences encoding the polypeptide or peptide. Methods which are well known to those skilled in the art can be used to construct expression vectors containing coding sequences and appropriate transcriptional and translational control signals. These methods include, for example, in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination. See, for example, the techniques described in Sambrook et al., 1989, supra, and Ausubel et al., 1989, supra. Alternatively, RNA capable of encoding CML progression protein polypeptide sequences may be chemically synthesized using, for example, synthesizers. See, for example, the techniques described in “Oligonucleotide Synthesis”, 1984, Gait, M. J. ed., IRL Press, Oxford, which is incorporated herein by reference in its entirety.

5.8.5 Chemotherapeutic Drugs

The invention can be practiced with any known chemotherapeutic drugs, including but not limited to DNA damaging agents, anti-metabolites, anti-mitotic agents, or a combination of two or more of such known anti-cancer agents.

DNA damage agents cause chemical damage to DNA and/or RNA. DNA damage agents can disrupt DNA replication or cause the generation of nonsense DNA or RNA. DNA damaging agents include but are not limited to topoisomerase inhibitor, DNA binding agent, and ionizing radiation. A topoisomerase inhibitor that can be used in conjunction with the invention can be a topoisomerase I (Topo I) inhibitor, a topoisomerase II (Topo II) inhibitor, or a dual topoisomerase I and II inhibitor. A topo I inhibitor can be for example from any of the following classes of compounds: camptothecin analogue (e.g., karenitecin, aminocamptothecin, lurtotecan, topotecan, irinotecan, BAY 56-3722, rubitecan, GI14721, exatecan mesylate), rebeccamycin analogue, PNU 166148, rebeccamycin, TAS-103, camptothecin (e.g., camptothecin polyglutamate, camptothecin sodium), intoplicine, ecteinascidin 743, J-107088, pibenzimol. Examples of preferred topo I inhibitors include but are not limited to camptothecin, topotecan (hycaptamine), irinotecan (irinotecan hydrochloride), belotecan, or an analogue or derivative of any of the foregoing.

A topo II inhibitor that can be used in conjunction with the invention can be for example from any of the following classes of compounds: anthracycline antibiotics (e.g., carubicin, pirarubicin, daunorubicin citrate liposomal, daunomycin, 4-iodo-4-doxydoxorubicin, doxorubicin, n,n-dibenzyl daunomycin, morpholinodoxorubicin, aclacinomycin antibiotics, duborimycin, menogaril, nogalamycin, zorubicin, epirubicin, marcellomycin, detorubicin, annamycin, 7-cyanoquinocarcinol, deoxydoxorubicin, idarubicin, GPX-100, MEN-10755, valrubicin, KRN5500), epipodophyllotoxin compound (e.g., podophyllin, teniposide, etoposide, GL331, 2-ethylhydrazide), anthraquinone compound (e.g., ametantrone, bisantrene, mitoxantrone, anthraquinone), ciprofloxacin, acridine carboxamide, amonafide, anthrapyrazole antibiotics (e.g., teloxantrone, sedoxantrone trihydrochloride, piroxantrone, anthrapyrazole, losoxantrone), TAS-103, fostriecin, razoxane, XK469R, XK469, chloroquinoxaline sulfonamide, merbarone, intoplicine, elsamitrucin, CI-921, pyrazoloacridine, elliptinium, amsacrine. Examples of preferred topo II inhibitors include but are not limited to doxorubicin (Adriamycin), etoposide phosphate (etopofos), teniposide, sobuzoxane, or an analogue or derivative of any of the foregoing.

DNA binding agents that can be used in conjunction with the invention include but are not limited to a DNA groove binding agent, e.g., DNA minor groove binding agent; DNA crosslinking agent; intercalating agent; and DNA adduct forming agent. A DNA minor groove binding agent can be an anthracycline antibiotic, mitomycin antibiotic (e.g., porfiromycin, KW-2149, mitomycin B, mitomycin A, mitomycin C), chromomycin A3, carzelesin, actinomycin antibiotic (e.g., cactinomycin, dactinomycin, actinomycin F1), brostallicin, echinomycin, bizelesin, duocarmycin antibiotic (e.g., KW 2189), adozelesin, olivomycin antibiotic, plicamycin, zinostatin, distamycin, MS-247, ecteinascidin 743, amsacrine, anthramycin, and pibenzimol, or an analogue or derivative of any of the foregoing.

DNA crosslinking agents include but are not limited to antineoplastic alkylating agent, methoxsalen, mitomycin antibiotic, psoralen. An antineoplastic alkylating agent can be a nitrosourea compound (e.g., cystemustine, tauromustine, semustine, PCNU, streptozocin, SarCNU, CGP-6809, carmustine, fotemustine, methylnitrosourea, nimustine, ranimustine, ethylnitrosourea, lomustine, chlorozotocin), mustard agent (e.g., nitrogen mustard compound, such as spiromustine, trofosfamide, chlorambucil, estramustine, 2,2,2-trichlorotriethylamine, prednimustine, novembichin, phenamet, glufosfamide, peptichemio, ifosfamide, defosfamide, nitrogen mustard, phenesterin, mannomustine, cyclophosphamide, melphalan, perfosfamide, mechlorethamine oxide hydrochloride, uracil mustard, bestrabucil, DHEA mustard, tallimustine, mafosfamide, aniline mustard, chlornaphazine; sulfur mustard compound, such as bischloroethylsulfide; mustard prodrug, such as TLK286 and ZD2767), ethylenimine compound (e.g., mitomycin antibiotic, ethylenimine, uredepa, thiotepa, diaziquone, hexamethylene bisacetamide, pentamethylmelamine, altretamine, carzinophilin, triaziquone, meturedepa, benzodepa, carboquone), alkylsulfonate compound (e.g., dimethylbusulfan, Yoshi-864, improsulfan, piposulfan, treosulfan, busulfan, hepsulfam), epoxide compound (e.g., anaxirone, mitolactol, dianhydrogalactitol, teroxirone), miscellaneous alkylating agent (e.g., ipomeanol, carzelesin, methylene dimethane sulfonate, mitobronitol, bizelesin, adozelesin, piperazinedione, VNP40101M, asaley, 6-hydroxymethylacylfulvene, EO9, etoglucid, ecteinascidin 743, pipobroman), platinum compound (e.g., ZD0473, liposomal-cisplatin analogue, satraplatin, BBR 3464, spiroplatin, ormaplatin, cisplatin, oxaliplatin, carboplatin, lobaplatin, zeniplatin, iproplatin), triazene compound (e.g., imidazole mustard, CB10-277, mitozolomide, temozolomide, procarbazine, dacarbazine), picoline compound (e.g., penclomedine), or an analogue or derivative of any of the foregoing. Examples of preferred alkylating agents include but are not limited to cisplatin, dibromodulcitol, fotemustine, ifosfamide (ifosfamid), ranimustine (ranomustine), nedaplatin (latoplatin), bendamustine (bendamustine hydrochloride), eptaplatin, temozolomide (methazolastone), carboplatin, altretamine (hexamethylmelamine), prednimustine, oxaliplatin (oxalaplatinum), carmustine, thiotepa, leusulfon (busulfan), lobaplatin, cyclophosphamide, bisulfan, melphalan, and chlorambucil, or an analogue or derivative of any of the foregoing.

Intercalating agents can be an anthraquinone compound, bleomycin antibiotic, rebeccamycin analogue, acridine, acridine carboxamide, amonafide, rebeccamycin, anthrapyrazole antibiotic, echinomycin, psoralen, LU 79553, BW A773U, crisnatol mesylate, benzo(a)pyrene-7,8-diol-9,10-epoxide, acodazole, elliptinium, pixantrone, or an analogue or derivative of any of the foregoing.

DNA adduct forming agents include but are not limited to enediyne antitumor antibiotic (e.g., dynemicin A, esperamicin A1, zinostatin, dynemicin, calicheamicin gamma II), platinum compound, carmustine, tamoxifen (e.g., 4-hydroxy-tamoxifen), psoralen, pyrazine diazohydroxide, benzo(a)pyrene-7,8-diol-9,10-epoxide, or an analogue or derivative of any of the foregoing.

Anti-metabolites block the synthesis of nucleotides or deoxyribonucleotides, which are necessary for making DN, thereby preventing cells from replicating. Anti-metabolites include but are not limited to cytosine, arabinoside, floxuridine, 5-fluorouracil (5-FU), mercaptopurine, gemcitabine, hydroxyurea (HU), and methotrexate (MTX).

Anti-mitotic agents disrupt the the development of the mitotic spindle thereby interfering with tumor cell proliferation. Anti-mitotic agents include but are not limited to Vinblastine, Vincristine, and Pacitaxel (Taxol). Anti-mitotic agents also includes agents that target the enzymes that regulate mitosis, e.g., agents that target kinesin spindle protein (KSP), e.g., L-001000962-000Y.

5.9. Kits

The invention provides kits that are useful in determining the stage of CML in a patient. The kits of the present invention comprise one or more probes and/or primers for each of at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 gene products that are encoded by the respectively marker genes listed in Tables 1a and/or 1b or functional equivalents of such genes, wherein the probes and/or primers are at least 50%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% of the total probes and/or primers in the kit. The probes of marker genes may be part of an array, or the biomarker(s) may be packaged separately and/or individually.

The invention provides kits that are useful in determining the progression of CML in a patient. The kits of the present invention comprise one or more probes and/or primers for each of at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 gene products that are encoded by the respectively marker genes listed in Tables 2a and/or 2b or functional equivalents of such genes, wherein the probes and/or primers are at least 50%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% of the total probes and/or primers in the kit. In a preferred embodiment, the kits comprise one or more probes and/or primers for each of at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 gene products that are encoded by the respectively marker genes listed in Table 4 or functional equivalents of such genes, wherein the probes and/or primers are at least 50%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% of the total probes and/or primers in the kit. The probes of marker genes may be part of an array, or the biomarker(s) may be packaged separately and/or individually.

In one embodiment, the invention provides kits comprising probes that are immobilized at an addressable position on a substrate, e.g., in a microarray. In a particular embodiment, the invention provides such a microarray.

The kits of the present invention may also contain probes that can be used to detect protein products of the marker genes of the invention. In a specific embodiment, the invention provides a kit comprises a plurality of antibodies that specifically bind a plurality of at least 5, 10, 20, 30, 40, 50, 60, 70, 80, or 100 proteins that are encoded by the respectively marker genes listed in Tables 1a and/or 1b or any one of Tables 2a and/or 2b and 5a and/or 5b or functional equivalents of such genes, wherein the antibodies are at least 50%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% of the total antibodies in the kit. In accordance with this embodiment, the kit may comprise a set of antibodies or functional fragments or derivatives thereof (e.g., Fab, F(ab′)₂, Fv, or scFv fragments). In accordance with this embodiment, the kit may include antibodies, fragments or derivatives thereof (e.g., Fab, F(ab′)₂, Fv, or scFv fragments) that are specific for these proteins. In one embodiment, the antibodies may be detectably labeled.

The kits of the present invention may also include reagents such as buffers, or other reagents that can be used in obtaining the marker profile. Prevention of the action of microorganisms can be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid, and the like. It may also be desirable to include isotonic agents such as sugars, sodium chloride, and the like.

In some embodiments of the invention, the kits of the present invention comprise a microarray. The microarray can be any of the microarrays described above, e.g., in Section 5.6.1, optionally in a sealed container. In one embodiment this microarray comprises a plurality of probe spots, wherein at least 20%, 40%, 60%, 80%, or 90% of the probe spots in the plurality of probe spots correspond to marker genes listed in Tables 1a and/or 1b or any one of Tables 2a and/or 2b and 4.

In still other embodiments, the kits of the invention may further comprise a computer program product for use in conjunction with a computer system, wherein the computer program product comprises a computer readable storage medium and a computer program mechanism embedded therein. In such kits, the computer program mechanism comprises instructions for prediction of prognosis using a marker profile obtained with the reagents of the kits.

In still other embodiments, the kits of the present invention comprise a computer having a central processing unit and a memory coupled to the central processing unit. The memory stores instructions for for prediction of prognosis using a marker profile obtained with the reagents of the kits.

5.10. Pharmaceutical Formulations and Routes of Administration

The compounds that can be used to modulate the expression of the CML progression genes or the activity of their gene products can be administered to a patient at therapeutically effective doses. A therapeutically effective dose refers to that amount of the compound sufficient to result in normal expression or activity level.

5.10.1. Effective Dose

Toxicity and therapeutic efficacy of such compounds can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., for determining the LD₅₀ (the dose lethal to 50% of the population) and the ED₅₀ (the dose therapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio LD₅₀/ED₅₀. Compounds which exhibit large therapeutic indices are preferred. While compounds that exhibit toxic side effects may be used, care should be taken to design a delivery system that targets such compounds to the site of affected tissue in order to minimize potential damage to uninfected cells and, thereby, reduce side effects.

The data obtained from the cell culture assays and animal studies can be used in formulating a range of dosage for use in humans. The dosage of such compounds lies preferably within a range of circulating concentrations that include the ED₅₀ with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. For any compound used in the method of the invention, the therapeutically effective dose can be estimated initially from cell culture assays. A dose may be formulated in animal models to achieve a circulating plasma concentration range that includes the IC₅₀ (i.e., the concentration of the test compound which achieves a half-maximal inhibition of symptoms) as determined in cell culture. Such information can be used to more accurately determine useful doses in humans. Levels in plasma may be measured, for example, by high performance liquid chromatography.

5.10.2. Formulations and Use

Pharmaceutical compositions for use in accordance with the present invention may be formulated in conventional manner using one or more pharmaceutically acceptable carriers or excipients.

Thus, the compounds and their pharmaceutically acceptable salts and solvates may be formulated for administration by inhalation or insufflation (either through the mouth or the nose) or oral, buccal, parenteral or rectal administration.

For oral administration, the pharmaceutical compositions may take the form of, for example, tablets or capsules prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e.g., pregelatinised maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose); fillers (e.g., lactose, microcrystalline cellulose or calcium hydrogen phosphate); lubricants (e.g., magnesium stearate, talc or silica); disintegrants (e.g., potato starch or sodium starch glycolate); or wetting agents (e.g., sodium lauryl sulphate). The tablets may be coated by methods well known in the art. Liquid preparations for oral administration may take the form of, for example, solutions, syrups or suspensions, or they may be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e.g., sorbitol syrup, cellulose derivatives or hydrogenated edible fats); emulsifying agents (e.g., lecithin or acacia); non-aqueous vehicles (e.g., almond oil, oily esters, ethyl alcohol or fractionated vegetable oils); and preservatives (e.g., methyl or propyl-p-hydroxybenzoates or sorbic acid). The preparations may also contain buffer salts, flavoring, coloring and sweetening agents as appropriate.

Preparations for oral administration may be suitably formulated to give controlled release of the active compound.

For buccal administration the compositions may take the form of tablets or lozenges formulated in conventional manner.

For administration by inhalation, the compounds for use according to the present invention are conveniently delivered in the form of an aerosol spray presentation from pressurized packs or a nebuliser, with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol the dosage unit may be determined by providing a valve to deliver a metered amount. Capsules and cartridges of e.g. gelatin for use in an inhaler or insufflator may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch.

The compounds may be formulated for parenteral administration by injection, e.g., by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multi-dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents. Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use.

The compounds may also be formulated in rectal compositions such as suppositories or retention enemas, e.g., containing conventional suppository bases such as cocoa butter or other glycerides.

In addition to the formulations described previously, the compounds may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection. Thus, for example, the compounds may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt.

The compositions may, if desired, be presented in a pack or dispenser device which may contain one or more unit dosage forms containing the active ingredient. The pack may for example comprise metal or plastic foil, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration.

5.10.3. Routes of Administration

Suitable routes of administration may, for example, include oral, rectal, transmucosal, transdermal, or intestinal administration; parenteral delivery, including intramuscular, subcutaneous, intramedullary injections, as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal, or intraocular injections.

Alternately, one may administer the compound in a local rather than systemic manner, for example, via injection of the compound directly into an affected area, often in a depot or sustained release formulation.

Furthermore, one may administer the drug in a targeted drug delivery system, for example, in a liposome coated with an antibody specific for affected cells. The liposomes will be targeted to and taken up selectively by the cells.

5.10.4. Packaging

The compositions may, if desired, be presented in a pack or dispenser device which may contain one or more unit dosage forms containing the active ingredient. The pack may for example comprise metal or plastic foil, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration. Compositions comprising a compound formulated in a compatible pharmaceutical carrier may also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition. Suitable conditions indicated on the label may include treatment of a disease such as one characterized by aberrant or excessive expression or activity of a CML progression protein.

5.10.5. Combination Therapy

In a combination therapy, one or more compositions of the present invention can be administered before, at the same time as, or after the administration of a chemotherapeutic agent. In one embodiment, the compositions of the invention are administered before the administration of an chemotherapeutic agent (i.e., the agent that modulates expression or activity of a CML progression gene or imatinib mesylate resistance gene and/or encoded protein is for sequential or concurrent use with one or more chemotherapeutic agents). In one embodiment, the composition of the invention and a chemotherapeutic agent are administered in a sequence and within a time interval such that the composition of the invention and a chemotherapeutic agent can act together to provide an increased benefit than if they were administered alone. In another embodiment, the composition of the invention and a chemotherapeutic agent are administered sufficiently close in time so as to provide the desired therapeutic outcome. The time intervals between the administration of the compositions of the invention and a chemotherapeutic agent can be determined by routine experiments that are familiar to one skilled person in the art. In one embodiment, a chemotherapeutic agent is given to the patient after the level of the CML progression gene or imatinib mesylate resistance gene and/or encoded protein reaches a desirable threshold. The level of a CML progression gene or imatinib mesylate resistance gene and/or encoded protein can be determined by using any techniques known in the art such as those described in Section 5.3., infra.

The composition of the invention and a chemotherapeutic agent can be administered simultaneously or separately, in any appropriate form and by any suitable route. In one embodiment, the composition of the invention and the chemotherapeutic agent are administered by different routes of administration. In an alternate embodiment, each is administered by the same route of administration. The composition of the invention and the chemotherapeutic agent can be administered at the same or different sites, e.g. arm and leg.

In various embodiments, such as those described above, the composition of the invention and a chemotherapeutic agent are administered less than 1 hour apart, at about 1 hour apart, 1 hour to 2 hours apart, 2 hours to 3 hours apart, 3 hours to 4 hours apart, 4 hours to 5 hours apart, 5 hours to 6 hours apart, 6 hours to 7 hours apart, 7 hours to 8 hours apart, 8 hours to 9 hours apart, 9 hours to 10 hours apart, 10 hours to 11 hours apart, 11 hours to 12 hours apart, no more than 24 hours apart or no more than 48 hours apart, or no more than 1 week or 2 weeks or 1 month or 3 months apart. As used herein, the word about means within 10%. In other embodiments, the composition of the invention and a chemotherapeutic agent are administered 2 to 4 days apart, 4 to 6 days apart, 1 week apart, 1 to 2 weeks apart, 2 to 4 weeks apart, one month apart, 1 to 2 months apart, or 2 or more months apart. In preferred embodiments, the composition of the invention and a chemotherapeutic agent are administered in a time frame where both are still active. One skilled in the art would be able to determine such a time frame by determining the half life of each administered component. In separate or in the foregoing embodiments, the composition of the invention and a chemotherapeutic agent are administered less than 2 weeks, one month, six months, 1 year or 5 years apart.

In another embodiment, the compositions of the invention are administered at the same time or at the same patient visit, as the chemotherapeutic agent.

In still another embodiment, one or more of the compositions of the invention are administered both before and after the administration of a chemotherapeutic agent. Such administration can be beneficial especially when the chemotherapeutic agent has a longer half life than that of the one or more of the composition of the invention used in the treatment.

In one embodiment, the chemotherapeutic agent is administered daily and the composition of the invention is administered once a week for the first 4 weeks, and then once every other week thereafter. In one embodiment, the chemotherapeutic agent is administered daily and the composition of the invention is administered once a week for the first 8 weeks, and then once every other week thereafter.

In certain embodiments, the composition of the invention and the chemotherapeutic agent are cyclically administered to a subject. Cycling therapy involves the administration of the composition of the invention for a period of time, followed by the administration of a chemotherapeutic agent for a period of time and repeating this sequential administration. Cycling therapy can reduce the development of resistance to one or more of the therapies, avoid or reduce the side effects of one of the therapies, and/or improve the efficacy of the treatment. In such embodiments, the invention contemplates the alternating administration of the composition of the invention followed by the administration of a chemotherapeutic agent 4 to 6 days later, preferable 2 to 4 days, later, more preferably 1 to 2 days later, wherein such a cycle may be repeated as many times as desired.

In certain embodiments, the composition of the invention and a chemotherapeutic agent are alternately administered in a cycle of less than 3 weeks, once every two weeks, once every 10 days or once every week. In a specific embodiment of the invention, one cycle can comprise the administration of a chemotherapeutic agent by infusion over 90 minutes every cycle, 1 hour every cycle, or 45 minutes every cycle. Each cycle can comprise at least 1 week of rest, at least 2 weeks of rest, at least 3 weeks of rest. In an embodiment, the number of cycles administered is from 1 to 12 cycles, more typically from 2 to 10 cycles, and more typically from 2 to 8 cycles.

It will be apparent to one skilled person in the art that any combination of different timing of the administration of the compositions of the invention and a chemotherapeutic agent can be used. For example, when the chemotherapeutic agent has a longer half life than that of the composition of the invention, it is preferable to administer the compositions of the invention before and after the administration of the chemotherapeutic agent.

The frequency or intervals of administration of the compositions of the invention depends on the desired level of the CML progression gene or imatinib mesylate resistance gene and/or encoded protein, which can be determined by any of the techniques known in the art, e.g., those techniques described infra. The administration frequency of the compositions of the invention can be increased or decreased when the level of the CML progression gene or imatinib mesylate resistance gene and/or encoded protein changes either higher or lower from the desired level.

5.11. Implementation Systems and Methods

The analytical methods of the present invention can preferably be implemented using a computer system, such as the computer system described in this section, according to the following programs and methods. Such a computer system can also preferably store and manipulate measured signals obtained in various experiments that can be used by a computer system implemented with the analytical methods of this invention. Accordingly, such computer systems are also considered part of the present invention.

An exemplary computer system suitable from implementing the analytic methods of this invention is illustrated in FIG. 8. Computer system 801 is illustrated here as comprising internal components and as being linked to external components. The internal components of this computer system include one or more processor elements 802 interconnected with a main memory 803. For example, computer system 801 can be an Intel Pentium IV®-based processor of 2 GHZ or greater clock rate and with 256 MB or more main memory. In a preferred embodiment, computer system 801 is a cluster of a plurality of computers comprising a head “node” and eight sibling “nodes,” with each node having a central processing unit (“CPU”). In addition, the cluster also comprises at least 128 MB of random access memory (“RAM”) on the head node and at least 256 MB of RAM on each of the eight sibling nodes. Therefore, the computer systems of the present invention are not limited to those consisting of a single memory unit or a single processor unit.

The external components can include a mass storage 804. This mass storage can be one or more hard disks that are typically packaged together with the processor and memory. Such hard disk are typically of 10 GB or greater storage capacity and more preferably have at least 40 GB of storage capacity. For example, in a preferred embodiment, described above, wherein a computer system of the invention comprises several nodes, each node can have its own hard drive. The head node preferably has a hard drive with at least 10 GB of storage capacity whereas each sibling node preferably has a hard drive with at least 40 GB of storage capacity. A computer system of the invention can further comprise other mass storage units including, for example, one or more floppy drives, one more CD-ROM drives, one or more DVD drives or one or more DAT drives.

Other external components typically include a user interface device 805, which is most typically a monitor and a keyboard together with a graphical input device 806 such as a “mouse.” The computer system is also typically linked to a network link 807 which can be, e.g., part of a local area network (“LAN”) to other, local computer systems and/or part of a wide area network (“WAN”), such as the Internet, that is connected to other, remote computer systems. For example, in the preferred embodiment, discussed above, wherein the computer system comprises a plurality of nodes, each node is preferably connected to a network, preferably an NFS network, so that the nodes of the computer system communicate with each other and, optionally, with other computer systems by means of the network and can thereby share data and processing tasks with one another.

Loaded into memory during operation of such a computer system are several software components that are also shown schematically in FIG. 8. The software components comprise both software components that are standard in the art and components that are special to the present invention. These software components are typically stored on mass storage such as the hard drive 804, but can be stored on other computer readable media as well including, for example, one or more floppy disks, one or more CD-ROMs, one or more DVDs or one or more DATs. Software component 810 represents an operating system which is responsible for managing the computer system and its network interconnections. The operating system can be, for example, of the Microsoft Windows™ family such as Windows 95, Window 98, Windows NT, Windows 2000 or Windows XP. Alternatively, the operating software can be a Macintosh operating system, a UNIX operating system or a LINUX operating system. Software components 811 comprises common languages and functions that are preferably present in the system to assist programs implementing methods specific to the present invention. Languages that can be used to program the analytic methods of the invention include, for example, C and C++, FORTRAN, PERL, HTML, JAVA, and any of the UNIX or LINUX shell command languages such as C shell script language. The methods of the invention can also be programmed or modeled in mathematical software packages that allow symbolic entry of equations and high-level specification of processing, including specific algorithms to be used, thereby freeing a user of the need to procedurally program individual equations and algorithms. Such packages include, e.g., Matlab from Mathworks (Natick, Mass.), Mathematica from Wolfram Research (Champaign, Ill.) or S-Plus from MathSoft (Seattle, Wash.).

Software component 812 comprises any analytic methods of the present invention described supra, preferably programmed in a procedural language or symbolic package. For example, software component 812 preferably includes programs that cause the processor to implement steps of accepting a plurality of measured signals and storing the measured signals in the memory. For example, the computer system can accept measured signals that are manually entered by a user (e.g., by means of the user interface). More preferably, however, the programs cause the computer system to retrieve measured signals from a database. Such a database can be stored on a mass storage (e.g., a hard drive) or other computer readable medium and loaded into the memory of the computer, or the compendium can be accessed by the computer system by means of the network 807.

In addition to the exemplary program structures and computer systems described herein, other, alternative program structures and computer systems will be readily apparent to the skilled artisan. Such alternative systems, which do not depart from the above described computer system and programs structures either in spirit or in scope, are therefore intended to be comprehended within the accompanying claims.

6. EXAMPLES

The following examples are presented by way of illustration of the present invention, and are not intended to limit the present invention in any way.

6.1. Identification of Phase-Specific Genes in CML

A set of 91 individual cases of CML, including chronic phase (N=42), accelerated phase by blast count criteria (N=9) or by the occurrence of additional clonal cytogenetic changes (N=8), blast crisis (N=28), and 4 cases of blast crisis in remission after chemotherapy were used to identify genes involved in progression from chronic phase to advanced disease (i.e., accelerated and blast phases). A pool of 200 chronic phase bone marrows was used as the reference. An ANOVA analysis revealed ˜3,000 genes differentially expressed across the different phases of disease using a minimum statistical significance cutoff of p<10⁻¹¹ (Tables 1a and 1b). Sequences of polynucleotide probes used to detect these genes are listed in Table 8. This set of genes identified in the progression from chronic to blast phase is referred to here as the “phase reporter” gene set. FIG. 1 shows a “heat map” of the expression of the 3,000 phase reporter genes across the various phases of CML. This illustrates the global change of gene expression as the disease progresses from the chronic phase through the advanced phase of the disease.

The expression patterns were then examined to determine if progression of CML best fits a three-step model as often described in the literature (chronic phase to accelerated phase to blast crisis), or a two-step model (chronic phase to advanced phase, i.e., accelerated or blast phase). The gene expression patterns of accelerated phase cases were compared to those of the blast crisis cases (FIG. 5). The correlation between the expression profiles of accelerated cases and those of the blast phase was quite strong (r=0.81). Comparing differentially regulated genes between accelerated phase with blast phase, there are very few phase specific genes, i.e. genes only regulated in one phase but not in another. These observations suggest that the difference of gene expression changes between accelerated and blast phase is a quantitative one rather than a qualitative one that requires new gene expression or repression.

The biological functions of the genes associated with CML phases were also examined by applying a biological annotation program based on the GO and KEGG annotations. The functional groups most highly correlated with progression to blast crisis included increased expression of nuclear genes, mitochondrial genes, RNA binding genes, protein biosynthesis genes, and genes involved in chaperone function, all reflecting the increased proliferation and metabolism of progressive disease.

Progression was also associated with decreases in the expression levels of genes involved in structural integrity and adhesion, as well as decreases in the expression levels of genes involved in inflammatory and immune response. In addition, several proto-oncogenes and tumor suppressor genes were differentially expressed with progression. For example, N- and Hras, FLT3, yes, AF1q, CBFB, WT1, ORALOV1, PTNN11, and Bcl-2 demonstrated increased expression in blast crisis as compared to chronic phase. Analysis of the phase reporter genes suggested a relative decrease in MAPPK signaling in advanced phase as compared to chronic phase. The progression was also seen as associated with increases in alternative signal pathways. Thus, the cytoplasmic GTP protein Rras2 was highly over-expressed in advanced phases, as was ras signaling components RAB56 and RALGD5. Alterations of cytokine signaling were demonstrated by an increase in expression of TNF factors SF4 and 7, and SOCS2 and 4.

6.2. Identification of Progression- and Response-Specific Genes

Next, how the phase reporter gene set was influenced by the gene expression signature of leukemia blasts and how they compared to normal immature CD34+ cells were investigated. First, the gene expression signatures of eight samples of normal CD34+ cells were compared with CML blast samples containing >70% blasts (FIG. 2 a). It was found that the gene expression pattern of CML blast cells was very similar to normal CD34+ cells, suggesting that “progression” from the chronic phase to the advanced phase is functionally similar to a block or “reversion” towards a more primitive hematopoetic cell. To uncover genes that are unique to progression, the normal CD34+ signatures were mathematically subtracted from each of the disease samples and the phase reporter signals were searched for (FIG. 2 c and FIG. 6). A set of 386 genes (p<10⁻⁸) were identified (FIG. 2 c and Tables 2a and 2b). These genes are called the “progression genes.” A set of 368 genes with ANOVA p<0.1% were identified as differentially expressed between CML blast crisis and normal immature CD34+ cells were also identified (FIG. 2 b and Tables 5a and 5b). These genes are called the “target genes.” There were 103 genes overlapping between these two sets (hypergeometric P-value: 1.3×10⁻⁹⁹). This gene set is enriched in genes that are diagnostic markers of progression and novel targets of therapy. Table 3 shows the “top ten” genes that are associated with progression, independent of normal CD34+ expression, based on log 10 ratio of expression compared to the chronic phase pool. These genes suggest a deregulation of genes of transcriptional regulation (GLI2, WT1, FOS, FOSB), signal transduction (SOCS2, Rras2, IL8), and apoptosis (GAS2). Moreover, two HSP 70 subunits are differentially down-regulated, suggesting an alteration of this component of the chaperone system in blast crisis. Also significantly associated with progression was the surface protein PRAME, which has an unknown function, but has been associated with myeloid malignancy (van Baren et al. 1998, Br J Haematol 102:1376; Watari et al. 2000, FEBS Lett 466:367). Gene functions overrepresented in blast crisis were predominated by changes in ribosome gene expression and increased in the beta-catenin/WNT signaling pathway. More significant changes in gene function were down-regulated in progression, including nucleosome assembly and chromatin structure, sugar catabolism and metabolism, differentiation, and apoptosis.

6.3. Identification of Signaling Pathways Associated with Progression

Multiple changes in several signaling pathways are represented in the progression gene set. Again, these genes were seen in the progression of chronic phase to advanced disease, but are differentially expressed compared to normal CD34+ cells. There was a deregulation of the betacatenin/WNT pathway. Expression of the cell surface protein cadherin was decreased, as was proto-cadhedrin, potentially leading to an activation of the beta-catenin/WNT signaling pathway by allowing more free beta-catenin to move to the cytoplasm. Moreover, the myogenesis transcription control gene MDFI (I-mfa), which complexes with axin (therefore potentially increasing free beta-catenin), was increased by approximately 7-fold. In all, 16 genes associated with the beta-catenin pathway were significantly over-expressed (e.g., PRICKLE1, CSNK1E, PLCB1, FZD2, LRP6, SMAD3, etc.). In summary, these findings strongly suggest aberrant activation of the betacatenin/WNT pathway during CML progression. Moreover, progression appears to be associated with a remodeling of several cytoskeletal and adhesion molecules, which may play a role in regulating proliferation. Thus there is an increase in CD47, Crebl1, and ITGA5 expression, and a decrease in proto-cadhedrin, cadhedrin, actin, and betaactin.

In addition, the abl family member abl2 (ARG) was significantly associated with disease progression; by contrast, abl1, which is both expressed from the normal chromosome 9 and the t(9;22) translocation, was not differentially expressed with progression. Advanced phase disease was associated with deregulation of transcription factors, differentiation and apoptosis. Both components of the AP-1 transcription complex, Jun B and Fos, show decreased expression in progression. In addition, the Kupple-like zinc finger GLI2 is highly over-expressed in progression. The block in differentiation may be facilitated by the up-regulation of MDFI, WT1, and AF1q, and the down regulation of GADD45. Apoptosis in blast cells appears to be inhibited by the over-expression of Bcl2, DAP, and the decrease in MCL1 and Acinus. Progression was also associated with alterations in normal protein chaperone and degradation processes, with a widespread decrease in the expression of HSP70 and DNAJ families of genes. In addition, proteosome components BMA1 PSME2, and TRIP12 were all significantly increased in advanced phase CML cases.

6.4. Identification of Progression-Specific Promoters

In order to examine if specific pathways were altered in progression, the progression and phase reporter gene sets were analyzed for aberrant expression of genes possessing known promoter sequences. Aberrant regulation of several sets of promoter controlled genes was revealed (Table 6). The most statistically significantly set of genes showing aberrant control in progression where those that contained a MZF promoter or a delta EF1 promoter sequence (p<10⁻¹⁵ and <10⁻¹¹, respectively; FIGS. 3 a and 3 b). Also significantly associated with progression were genes bearing SPI-B, Yin Yang, and Ahr-ARNT promoter sequences (all with p values <10⁻⁹).

6.5. Identification of Imatinib Responsiveness Reporter Genes

Gene expression profiles of patients who failed imatinib therapy were analyzed. A set of 21 cases of CML treated with the tyrosine kinase inhibitor imatinib mesylate, including 9 patients who initially achieved a complete cytogenetic remission (CCR) on imatinib therapy, but then relapsed, most back into an apparent chronic phase by morphology; 3 cases who had achieved a complete hematologic but no cytogenetic response; 3 late chronic phase patients before treatment with imatinib; and 6 cases of blast crisis was used. All but one of these the chronic phase patients who relapsed after a CCR had a point mutation in abl1, presumably abrogating imatinib activity (Table 7).

TABLE 7 Characteristics of cases treated with imatinib Phase of Disease at Phase of disease at CODE Case type initiation of imatinib time of sample Cytogenetics Mutation(s)  2 Imatinib failure chronic relapsed chronic 100% Ph+; M244V NEW: t(1; 12) in all cells  4 Imatinib failure chronic relapsed chronic 100% Ph+ T315I  5 Imatinib failure chronic relapsed chronic 80% Ph+ F359V  6 Imatinib failure chronic relapsed chronic 100% Ph+ M351T, F317L  8 Imatinib failure chronic relapsed chronic 100% Ph+ M351T 10 Imatinib failure chronic relapsed chronic 100% Ph+ E255K 11 Imatinib failure chronic post-allo relapsed chronic not available T315I BMT 12 Imatinib failure chronic relapsed chronic 100% Ph+ L248V 14 Imatinib failure chronic relapsed chronic 100% Ph+ M351T, H396R 15 Pre-imatinib chronic chronic pre-treatment 50% Ph+ none treatment 17 Pre-imatinib chronic chronic pre-treatment 100% Ph+ none treatment 18 Pre-imatinib chronic CHR; no cytogenetic 100% Ph+ none treatment response 19 Pre-imatinib chronic chronic pre-treatment 45% t(9; 13; 22); 50% none treatment t (9; 13; 22), −Y; 5% nl 21 Pre-imatinib chronic CHR; no cytogenetic 100% Ph+ none treatment response 22 (same pt as Pre-imatinib chronic CHR; no cytogenetic 100% Ph+ (3 of 18 none 13) treatment response with additional Ph) 23 Pre-imatinib myeloid blast crisis pre-treatment MBC 100% Ph+ none treatment 24 Pre-imatinib myeloid blast crisis pre-treatment MBC 100% Ph+, t(2; 16) none treatment 25 Pre-imatinib myeloid blast crisis pre-treatment MBC 100% Ph+, +8, iso none treatment 17q 26 Pre-imatinib myeloid blast crisis not treated not available unknown treatment 27 Pre-imatinib myeloid blast crisis relapsed MBC 100% Ph+ unknown treatment 29 Pre-imatinib myeloid blast crisis relapsed MBC not available unknown treatment 29 Pre-imatinib myeloid blast crisis relapsed MBC not available unknown treatment

FIG. 4 a shows the expression pattern of 15 cases of clinical chronic phase CML patients, 3 with longstanding chronic phase before imatinib treatment, the other 12 who had initially a suboptimal response (achieving only a hematological response) or relapsed after an initial CCR. The association with the progression signature can be demonstrated by segregating all CML cases by the correlation of gene expression signature between the boundaries of “most chronic” and “most advanced” gene expression for all 3,000 genes in the phase reporter gene set (FIG. 4 b). The majority of the poor response patients had gene expression profiles more consistent with advanced disease rather than chronic phase. Both cases with T315I mutations, which have been shown to have especially poor prognosis, have expression signatures more similar to advanced disease than chronic phase. However, while these imatinib failures shared much of the blast crisis signature, there were gene expression features that were unique to these cases. FIG. 4 c compares relapsed imatinib cases against blast crisis cases. Several areas (boxed) indicate genes that are expressed in reverse direction in these two states. Table 4 lists genes in the first box which are strongly associated with imatinib failure. Examples of genes unique to imatinib failure are those of serine threonine kinases (CTRL, MAP21K14, CLK3), MAP kinase (MKNK2), and the tyrosine kinase oncogene FYN. The highest genes over-expressed in imatinib resistant cases were TCF7 (a putatively T cell specific transcription factor), two guanine nucleotide binding proteins (GNAZ and GNG11), and the MAF oncogene.

6.6. Discussion

The biology and treatment of CML is dictated by the phase of disease, since the efficacy of all therapies (transplantation, interferon, imatinib) works best in chronic phase, and worse in accelerated phase and blast crisis. Understanding the biology of progression provides clinical diagnostic markers of progression, and offer insights into new strategies for treatment. The data presented in these examples suggest that the progression of chronic phase CML to advanced phase CML is a two-step process, with progression associated with a block of differentiation and apoptosis, a shift towards turning on expression of genes involved in the nucleosome, while down-regulating histone transcription. Moreover, progression is associated with alterations in cell adhesion, and activation of alternative signaling pathways. In addition, it appears that relapse after initial successful treatment with imatinib may be associated with gene expression patterns similar to advanced phase CML, suggesting that the process of progression persists in a subpopulation of CML cells even in the background of apparent successful therapy.

The demonstration that the gene expression pattern between accelerated and blast phases are very similar suggests that the crucial steps in progression are at the transition of chronic to accelerated phase, before obvious morphologic, cytogenetic or clinical evidence of progression. This has obvious clinical implications, since these patients might benefit from aggressive therapy. In addition, the observation that gene signatures of blast crisis can be seen in accelerated phase patients by cytogenetic criteria only, and blast crisis cases in remission (both of which have low blast counts similar to patients with chronic phase disease), demonstrates two important points. First, it points out the difficulty of correlating morphology with the biology of the disease.

Secondly, the penetration of a progression gene expression signature into a “chronic phase” appearing bone marrow suggests that progression is not merely an absolute block of differentiation, but that abnormal gene expression signals “leak” from the presumably immature blast crisis precursors into more normal appearing differentiated cell. This is critically important since it provides the basis for testing for progression genes in unsorted bone marrow samples from “chronic phase” patients.

In addition, the finding that CML blasts share a gene expression profile with normal CD34+ cells has important biological considerations (Passegue et al., 2003, Proc Natl Acad Sci USA 100 Suppl 1:11842). First, it implies that there may be a limited number of novel pathways active in CML blasts. This finding is obviously important (and encouraging) in the era of targeted therapeutics. It also may explain the relative resistance of blast crisis CML to chemotherapy. Normal hematopoetic stem cells are remarkably resistant to chemotherapy, and thus in AML and ALL, with remission comes the return of normal hematopoesis. Remission is rare in blast crisis CML, perhaps because the blast cells are similarly resistant to chemotherapy as their normal counterpart.

Bcr-Abl has a wholesale range of biological activities. Critical in the transformation process is the activation of the Ras/MAPK pathways, which has broad effects on changes in cell adhesion (through Rho), proliferation (MAPK pathway), and apoptosis (through Akt) (Faderl et al., 1999, N Engl J Med 341:164; Ren, 2002, Oncogene 21:8629). The efficacy of imatinib works through the blockade of these effects.

Imatinib works poorly on advanced phase disease, and it may be because these tumors are less reliant on the pathways that imatinib blocks than chronic phase disease. Thus, it was found that the MAPK pathway was relatively under-expressed in advanced disease compared to chronic phase, but other signaling pathways, including those involving cytokines (IL3RA, SOCS2), alternative ras pathways (Rras2), and those involved in cell adhesion (B-catenin/WNT) were activated. The activation of these pathways may allow progression even in the face of therapeutic blockade of Bcr-Abl activated pathways. In addition, abl2 (Abl related gene, or ARG) is also upregulated in progresson. As opposed to abl1 (which is a nuclear protein until involved in the chimeric Bcr-Abl protein, at which time it migrates to the cytoplasm), ARG is a cytoplasmic protein (Kruh et al., 1990, Proc Natl Acad Sci USA 87:5802). The signaling targets of ARG are unknown, and although broadly expressed in tissue, its only known functional role apparent from knockout mouse models appears to be in the nervous system (Koleske et al., 1998, Neuron 21:1259; Perego et al., 1991, Oncogene 6:1899). ARG has been associated with myeloid leukemia in the contest of TEL/ARG translocations (Cazzaniga et al., 1999, Blood 94:4370; Iijima et al., 2000, Blood 95:2126). ARG shares over 90% homology of its tyrosine kinase domain with abl1, and ARG tyrosine kinase activity is inhibited by imatinib at similar drug concentrations (Kruh et al., 1990, Proc Natl Acad Sci USA 87:5802; Okuda et al., 2001, Blood 97:2440). However, given that Bcr-ABL amplification is considered to play a role in imatinib resistance (le Coutre et al. 2000, Blood 95:1758; Weisberg et al., 2000, Blood 95:3498), ARG over-expression in blast crisis could theoretically contribute to the relative resistance to imatinib found with progressive disease.

Two recent observations on the molecular biology of progression in CML are relevant to this study. First, activation of the beta-catenin pathway was observed in primary cell samples from patients with CML (Jamieson et al., 2004, N Engl J Med 351:657). Secondly, it was recently observed that mice deficient in Jun B develop a disease much like CML (Passegue et al., 2004, Cell 119:431). The data in these examples complement these findings, as we found broad dysregulation of WNT/beta-catenin pathway as well as decreased Jun B expression. A link between these pathways may be the gene MDFI (Imfa), an inhibitor of myogenic basic H-L-H transcription factors 4. MDFI interacts with axin, which is involved in binding and modulating free beta-catenin. Thus an increase in MDFI would effectively allow for more free beta-catenin to migrate to the nucleus, where it causes gene activation (Nelson et al., 2004, Science 303:1483). An increase in MDFI could also decrease the axinmediated activation of Jun (Kusano et al., 2002, Mol Cell Biol 22:6393). Thus, MDFI may play a central role in progression by both influencing the beta-catenin and Jun B pathways. Moreover, the fact that both Jun B and Fos were down-regulated in progression suggests that there may be a wholesale deregulation in AP-1 targets, which could have broad functional affects on differentiation, apoptosis, and cell cycle control (Hess et al., 2004, J Cell Sci 117:5965).

The analysis suggests that genes controlled by MZF1 and delta EF1 may be particularly important in progression. MZF1 is a member of the Kruppel family of zinc finger proteins, and was originally cloned from a cDNA library from a blast crisis CML patient (Hromas et al., 1991, J Biol Chem 266:14183). MZF1 appears to play a critical role in hematopoetic stem cell differentiation, including modulation of CD34 and c-myb expression (Gaboli et al., 2001, Genes Dev 15:1625; Perrotti et al., 1995, Mol Cell Biol 15:6075). MZF1 −/− knock-out mice display an increase in hemapoetic progenitor proliferation which continues in long-term culture conditions (Gaboli et al., 2001, Genes Dev 15:1625). These data support the findings found in our human studies described about that MZF1 deregulation may disrupt normal differentiation, promoting the progression to advanced disease. Delta EF1 is related to the Smad zinc finger proteins that play an important role in TGFbeta gene regulation. Delta EF1 has been shown to compete with basic helix-loop-helix activators, and is implicated in modulation of MyoD regulated pathways (Funahashi et al., 1993, Development 119:433; Sekido et al., 1994, Mol Cell Biol 14:5692). It is not known if delta EF1 directly influences MDFI expression.

Of note is that both MZF1 and delta EF1 have been shown to influence cadherin expression (Guaita et al., 2002, J Biol Chem 277:39209; Le et al., 2005, Exp Cell Res 302:129; Miyoshi et al., 2004, Br J Cancer 90:1265). Thus, the further study of the control of MZF1 and delta EF1 may be particularly fruitful in understanding the molecular mechanisms of CML progression. Given that efficacy of treatment in CML (be it with interferon, imatinib, or transplantation) is so intimately associated with phase of disease, those patients who fail therapy in chronic phase may have genetic features of advanced phase invisible to routine pathological and cytogenetic exam. Imatinib failures are a reasonable setting to explore this possibility. While imatinib can cause cytogenetic remissions in the majority of chronic phase cases, treatment failure, especially secondary to point mutations, is an increasingly important problem. It has previously been demonstrated that the probability of developing a point mutation depends largely on the time from diagnosis to initiation of therapy (Branford et al., 2003, Blood 102:276). This finding implies that the genetic mechanisms that lead to point mutations are relentless, and therefore the treatment of “late” chronic phase patients (i.e., >1 year from diagnosis) may be undermined by genetic changes that have already occurred. Branford et al. demonstrated that patients who developed point mutations had a very poor outcome, with approximately half dying within a year of relapse (Branford et al., 2003, Blood 102:276). These observations are in keeping with the demonstration in these examples that many imatinib failures have gene expression changes similar to advanced disease, despite their benign pathological appearance. Thus, resistance to imatinib may be ameliorated by either targeting pathways of progression (beta-catenin, JunB/Fos, etc.), or by targeting pathways specifically found activated in imatinib resistance cases (alternative kinases, protein transporters).

Several of the genes found in the progression set might serve as early markers of progression in diagnostic assays, and may serve as therapeutic targets, as well. For example, PRAME (Preferentially Expressed Antigen of Melanoma) was originally identified as a tumor antigen recognized by cytotoxic T-cells against a melanoma surface antigen (Matsushita et al., 2001, Br J Haematol 112:916, 2001; van Baren et al., 1998, Br J Haematol 102:1376). Like similar antigens MAGE, BAGE, and GAGE, which are expressed in some solid tumors; unlike these other antigens, however, PRAME has been found to be overexpressed in over 25% of leukemia, and has been found to be induced by Bcr-Abl in CML cell lines (Watari et al., 2000, FEBS Lett 466:367). Indeed, PRAME over-expression has been described as one of the few features that characterize the transient myeloproliferative syndrome of Down's syndrome from the progressive acute megakaryoblastic leukemia found in that disorder (McElwaine et al., 2004, Br J Haematol 125:729). While the function of PRAME is still unknown, its expression on the cell surface might be amenable to flow cytometry assays, as well as a target for immunologic (vaccine or cell-based) therapy. CD47, an integrin-like protein, is another potential diagnostic target discovered in our analysis of progression (Motegi et al., 2003, Embo J 22:2634; Okazawa et al., 2005, J Immunol 174:2004). In addition, the demonstration of aberrant regulation of alternative signaling pathways (FLT3; Rras2; beta-catenin. SOCS2), proteosomes, and chaperone proteins suggest that the targeting of several novel pathways may be needed in the treatment of advanced CML.

Compared to other types of leukemia, there have been few papers exploring the use of microarrays on the biology of CML. In sum, 23 patients of various stages have been studied, 10 on unsorted samples, 13 from AC133+ isolated cells. It is difficult to make a direct comparison of these studies and ours, given the different types of samples obtained, the difference in the array platforms (these studies used platforms examining 3,000-5,000 genes, compared to ˜24,000 genes in this current study). In general, however, the functional changes of progression, e.g., changes in differentiation, apoptosis, and cell adhesion, remained as common themes across the study. In contrast to one study, no significant differences in signatures obtained from bone marrow and peripheral blood (FIG. 7) were found, which may be important in future prospective studies of this disease in patients.

These findings have the potential to influence therapy of CML. Patients who present with gene expression patterns suggestive of advanced phase disease might benefit to move straight to transplantation if a donor exists, or if not, other investigation therapies. Moreover, PCR assays of individual genes (or small sets of genes) may be used to monitor patients early in the course of imatinib therapy for signs of progression to advanced disease. Microarray studies of large cohorts of patients treated with imatinib will likely identify gene patterns indicative of response that can be used immediately at diagnosis to tailor therapy.

6.7. Materials and Methods

Patient samples. All samples were obtained under the auspices of institutional review board approve protocols. Samples came from the FHCRC, the Southwest Oncology Group (SWOG) Myeloid Repository, the University of Oregon Health Sciences Center, the University of California, Los Angeles, or the University of Chicago. RNA extraction was either performed immediately, or in the case of samples stored in a liquid nitrogen repository, after thawing. All RNA samples were quality tested by analysis of ribosomal RNA peaks using an ABI Bioalyzer. The definition of chronic, accelerated and blast crisis was based on the criteria of Sokal (Sokal et al., 1984, Blood 63:789).

Amplification, labeling, and hybridization. The procedures of RNA amplification, labeling, and the hybridization to arrays, as well as the specifics of the array platforms, has been previously published (Hughes et al., 2001, Nat Biotechnol 19:342).

Analytic Methods and Results. Each individual sample was hybridized to a pool of chronic phase samples. The log 10 (Ratio) of intensity of individual samples to the pool were used for the subsequent analysis. Before selecting features by ANOVA, 25,000 genes on the array were first screened for evidence of differential regulation by requiring P-value of regulation <1% in more than 3 experiments. Where P-value of regulation is based on the platform error model. Features differentiating progression stages were selected by ANOVA test.

Functional annotation of gene lists. Genes represented on the microarray were annotated by assignment to GO Biological Process or Molecular Function categories, or to KEGG pathways. Gene lists (input sets) were queried for enrichment of members of specific functional classes or pathways relative to the background frequency. The significance (P-value) of enrichment was computed using the hypergeometric probability distribution. Reported in each case are the numbers of genes in the input set (input gene count), number of genes in a particular category or pathway in the input set (overlap gene count), number of genes in a particular category among all genes present on the array (set gene count). The total number of unique genes on the array is 24132.

Methods to common promote site analysis. The common promoter sites were based on the predictions derived from the database (oPOSSUM) by Wasserman et al. (www.cisreg.ca). The hypergeometric P-value for enrichment of a particular binding site was computed by comparing the number of genes with the binding site from a signature gene set to that from a background set (i.e., all genes represented on the microarray).

Controls. We compared the genes found associated with progression to the genes found significantly over- and under-expressed with prolonged “transit time” from sample acquisition to RNA processing (Radich et al., 2004, Genomics 83:980). There gene signatures of the two data sets were different, excluding this artifact as contributing significantly to the progression gene set.

Lastly, we compared gene expression signatures from the sites contributing samples to confirm that there were no site-signatures confounding the analysis. We found no evidence of site-specific signatures.

As some samples of blast crisis came from peripheral blood rather than bone marrow, we compared three samples in which simultaneous samples were available from bone marrow and peripheral blood. Gene expression was extremely well correlated (r=0.97 to 0.99; FIG. 7).

TABLE 8 The phase reporter genes PROBE SEQ SEQ SUBS GENE DESCRIPTION SP_XREF_KEYWORD_LIST ID NO. ID NO. AB002301 KIAA0303 KIAA0303 protein Hypothetical protein, ATP-binding, 1 3969 Kinase, Serine/threonine-protein kinase, Transferase AB002313 PLXNB2 plexin B2 Hypothetical protein 2 3970 AB002314 KIAA0316 KIAA0316 gene Hypothetical protein 3 3971 product AB002331 DATF1 death associated Apoptosis, Nuclear protein, Zinc- 4 3972 transcription factor 1 finger, Alternative splicing AB002336 EPB41L1 erythrocyte Hypothetical protein, Structural 5 3973 membrane protein protein, Cytoskeleton, Actin-binding band 4.1-like 1 AB002337 KIAA0339 KIAA0339 gene Hypothetical protein 6 3974 product AB002354 KIAA0356 pleckstrin homology Hypothetical protein 7 3975 domain containing, family M (with RUN domain) member 1 AB002359 PFAS phosphoribosylformylglycinamidine Purine biosynthesis, Ligase, ATP- 8 3976 synthase (FGAR binding, Glutamine amidotransferase) amidotransferase, Hypothetical protein AB002360 MCF2L MCF.2 cell line Hypothetical protein, Guanine- 9 3977 derived transforming nucleotide releasing factor, Proto- sequence-like oncogene AB002366 KIAA0368 KIAA0368 Hypothetical protein 10 3978 AB002368 XPO6 exportin 6 Hypothetical protein 11 3979 AB002369 MTMR3 myotubularin related Hydrolase, Zinc-finger, Alternative 12 3980 protein 3 splicing, Hypothetical protein AB002373 KIAA0375 RUN and SH3 Hypothetical protein, SH3 domain 13 3981 domain containing 2 AB002377 KIAA0379 ankyrin repeat Hypothetical protein, Repeat, ANK 14 3982 domain 28 repeat AB002379 DAAM2 dishevelled Coiled coil, Alternative splicing 15 3983 associated activator of morphogenesis 2 AB004857 SLC11A2 solute carrier family Transport, Iron transport, 16 3984 11 (proton-coupled Transmembrane, Glycoprotein, divalent metal ion Alternative splicing, Polymorphism transporters), member 2 AB006622 KIAA0284 KIAA0284 Hypothetical protein 17 3985 AB007855 TIX1 zinc fingers and DNA-binding, Homeobox, Nuclear 18 3986 homeoboxes 3 protein, Zinc-finger, Metal-binding, Repeat AB007863 PIP3-E phosphoinositide- Hypothetical protein 19 3987 binding protein PIP3-E AB007864 KIAA0404 KIAA0404 protein Hypothetical protein, Metal-binding, 20 3988 Oxidoreductase, Zinc AB007888 MBNL1 muscleblind-like Hypothetical protein, Zinc-finger, 21 3989 (Drosophila) Repeat, Nuclear protein, RNA- binding, Alternative splicing AB007902 AUTS2 autism susceptibility Chromosomal translocation, 22 3990 candidate 2 Polymorphism, Alternative splicing AB007915 KIAA0446 KIAA0446 gene Hypothetical protein 23 3991 product AB007931 RBAF600 retinoblastoma- Hypothetical protein 24 3992 associated factor 600 AB007941 KIAA0472 dusty protein kinase ATP-binding, Transferase, 25 3993 Hypothetical protein, Kinase, Serine/threonine-protein kinase AB007958 KIAA0489 KIAA0792 gene Hypothetical protein 26 3994 product AB007962 KIAA0493 KIAA0493 protein 27 3995 AB007965 CYHR1 MRNA, chromosome 28 3996 1 specific transcript KIAA0496. AB007972 PPP1R12B protein phosphatase ANK repeat, Myosin, Repeat 29 3997 1, regulatory (inhibitor) subunit 12B AB011093 P114-RHO- rho/rac guanine Hypothetical protein 30 3998 GEF nucleotide exchange factor (GEF) 18 AB011105 LAMA5 laminin, alpha 5 Laminin EGF-like domain, Signal, 31 3999 Glycoprotein, Basement membrane, Extracellular matrix, Coiled coil, Cell adhesion, Repeat AB011112 KIAA0540 KIAA0540 protein Hypothetical protein, Repeat, WD 32 4000 repeat AB011114 KIAA0542 KIAA0542 gene Hypothetical protein 33 4001 product AB011133 KIAA0561 microtubule Hypothetical protein, ATP-binding, 34 4002 associated Kinase, Serine/threonine-protein serine/threonine kinase, Transferase kinase 3 AB011136 KIAA0564 KIAA0564 protein Hypothetical protein, ATP-binding 35 4003 AB011153 PLCB1 phospholipase C, Hydrolase, Lipid degradation, 36 4004 beta 1 Transducer, Phosphorylation, (phosphoinositide- Calcium, Alternative splicing specific) AB011154 RAB1A KIAA0582 protein Hypothetical protein 37 4005 AB011157 PTDSR phosphatidylserine Hypothetical protein, Receptor 38 4006 receptor AB011167 KIAA0595 peroxisome Hypothetical protein 39 4007 proliferative activated receptor, gamma, coactivator- related 1 AB011171 KIAA0599 KIAA0599 Hypothetical protein, Plasmid 40 4008 AB011173 KIAA0601 amine oxidase Hypothetical protein 41 4009 (flavin containing) domain 2 AB011542 EGFL5 EGF-like-domain, Laminin EGF-like domain 42 4010 multiple 5 AB012692 CAC-1 beta-casein-like Hypothetical protein 43 4011 protein AB014516 MECT1 Homo sapiens Transcription regulation, DNA- 44 4012 mRNA for KIAA0616 binding, Activator, Nuclear protein, protein, partial cds. Phosphorylation, Cell cycle, Alternative splicing, 3D-structure, Polymorphism, Hypothetical protein AB014520 PLXND1 plexin D1 Hypothetical protein 45 4013 AB014538 KIAA0638 pleckstrin homology- Hypothetical protein 46 4014 like domain, family B, member 1 AB014543 KIAA0643 KIAA0643 protein Hypothetical protein 47 4015 AB014548 KIAA0648 KIAA0648 protein Hypothetical protein 48 4016 AB014557 KIAA0657 KIAA0657 protein Hypothetical protein, 49 4017 Immunoglobulin domain AB014558 CRY2 cryptochrome 2 Lyase, Hypothetical protein 50 4018 (photolyase-like) AB014564 KIAA0664 KIAA0664 protein Hypothetical protein, Initiation factor, 51 4019 Protein biosynthesis AB014566 DAAM1 dishevelled Coiled coil, Alternative splicing 52 4020 associated activator of morphogenesis 1 AB014567 TIP120B TBP-interacting Hypothetical protein 53 4021 protein AB014568 UNC84B unc-84 homolog B Transmembrane, Nuclear protein, 54 4022 (C. elegans) Coiled coil AB014574 KIAA0674 KIAA0674 protein Hypothetical protein 55 4023 AB014578 KIAA0678 RME8 protein Hypothetical protein 56 4024 AB014589 CSTF2T cleavage stimulation Hypothetical protein 57 4025 factor, 3′ pre-RNA, subunit 2, 64 kDa, tau variant AB014597 GTAR ankyrin repeat Hypothetical protein, ANK repeat, 58 4026 domain 17 Repeat AB014600 SIN3B SIN3 homolog B, Transcription regulation, Repressor, 59 4027 transcriptional Repeat, Nuclear protein regulator (yeast) AB014604 OSBPL3 oxysterol binding Lipid transport, Transport, 60 4028 protein-like 3 Alternative splicing AB015330 DKFZP761I2123 hypothetical protein Hypothetical protein 61 4029 DKFZp761I2123 AB015343 HRIHFB2122 Tara-like protein Cytoskeleton, Actin-binding, Coiled 62 4030 coil, Nuclear protein AB018268 KIAA0725 SAM, WWE and Hypothetical protein 63 4031 DDHD domain containing 1 AB018325 CENTD2 centaurin, delta 2 GTPase activation, Repeat, Zinc- 64 4032 finger, Alternative splicing AB018339 SYNE1 spectrin repeat Structural protein, Cytoskeleton, 65 4033 containing, nuclear Actin-binding, Coiled coil, envelope 1 Transmembrane, Repeat, Alternative splicing, Polymorphism AB018348 PCNX pecanex homolog Transmembrane, Glycoprotein, 66 4034 (Drosophila) Alternative splicing AB018353 UNC84A unc-84 homolog A Transmembrane, Nuclear protein, 67 4035 (C. elegans) Coiled coil, Alternative splicing AB020627 KIAA0820 dynamin family Hydrolase, Motor protein, GTP- 68 4036 member binding, Microtubule, Multigene family, Endocytosis AB020636 TIP120A TBP-interacting Hypothetical protein 69 4037 protein AB020637 KIAA0830 KIAA0830 protein Hypothetical protein 70 4038 AB020644 FACL6 acyl-CoA synthetase Ligase, Fatty acid metabolism, 71 4039 long-chain family Magnesium, Multigene family, member 6 Alternative splicing, Chromosomal translocation, Hypothetical protein AB020649 KIAA0842 pleckstrin homology Hypothetical protein 72 4040 domain containing, family M (with RUN domain) member 2 AB020673 MYH11 myosin, heavy Myosin, Muscle protein, Coiled coil, 73 4041 polypeptide 11, Thick filament, Actin-binding, smooth muscle Calmodulin-binding, ATP-binding, Methylation, Multigene family, Proto- oncogene, Chromosomal translocation AB020684 KIAA0877 KIAA0877 protein Hypothetical protein 74 4042 AB020691 KIAA0884 GTPase activating Hypothetical protein 75 4043 RANGAP domain- like 1 AB020695 KIAA0888 KIAA0888 protein Hypothetical protein 76 4044 AB020698 USP19 ubiquitin specific Protease, Ubl conjugation pathway, 77 4045 protease 19 Hydrolase, Thiol protease, Multigene family, Zinc-finger, Metal-binding AB020703 DD5 progestin induced Ubl conjugation pathway, Ligase, 78 4046 protein Nuclear protein, 3D-structure AB020704 PPFIA4 protein tyrosine Hypothetical protein 79 4047 phosphatase, receptor type, f polypeptide (PTPRF), interacting protein (liprin), alpha 4 AB023152 KIAA0935 mannosidase alpha Hydrolase, Glycosidase, Signal, 80 4048 class 2B member 2 Glycoprotein, Hypothetical protein AB023154 KIAA0937 macrophage Hypothetical protein, Metal-binding, 81 4049 expressed gene 1 Zinc, Zinc-finger AB023156 SLC9A8 solute carrier family Hypothetical protein 82 4050 9 (sodium/hydrogen exchanger), isoform 8 AB023164 KIAA0947 KIAA0947 protein Hypothetical protein 83 4051 AB023210 WDFY3 WD repeat and Hypothetical protein, Repeat, WD 84 4052 FYVE domain repeat containing 3 AB023211 PADI2 peptidyl arginine Hydrolase, Calcium-binding, 85 4053 deiminase, type II Multigene family AB023212 PCNX pecanex homolog Transmembrane, Glycoprotein, 86 4054 (Drosophila) Alternative splicing AB023216 KIAA0999 KIAA0999 protein Hypothetical protein, ATP-binding, 87 4055 Kinase, Serine/threonine-protein kinase, Transferase AB023230 KIAA1013 GRP1-binding Hypothetical protein, Cytoskeleton 88 4056 protein GRSP1 AB023233 CHDC1 calponin homology Hypothetical protein, Leucine-rich 89 4057 (CH) domain repeat, Repeat containing 1 AB025254 PCTAIRE2BP tudor repeat Hypothetical protein 90 4058 associator with PCTAIRE 2 AB026054 ZNF179 zinc finger protein Zinc-finger 91 4059 179 AB026436 DUSP10 dual specificity Hydrolase, Nuclear protein, 92 4060 phosphatase 10 Hypothetical protein AB028972 KIAA1049 KIAA1049 protein Hypothetical protein 93 4061 AB028978 KIAA1055 KIAA1055 protein Hypothetical protein 94 4062 AB028980 USP24 ubiquitin specific Hypothetical protein, Ubl conjugation 95 4063 protease 24 pathway, Hydrolase, Thiol protease, Multigene family AB028986 USP22 ubiquitin specific Hypothetical protein, Protease, Ubl 96 4064 protease 22 conjugation pathway, Hydrolase, Thiol protease, Multigene family AB028989 MAPK8IP3 mitogen-activated Phosphorylation, Coiled coil 97 4065 protein kinase 8 interacting protein 3 AB028994 AMOT angiomotin Hypothetical protein 98 4066 AB029030 KIAA1107 KIAA1107 protein Hypothetical protein 99 4067 AB029032 FLJ21404 hypothetical protein Hypothetical protein 100 4068 KIAA1109 AB029041 KIAA1118 likely ortholog of Hypothetical protein 101 4069 mouse 5-azacytidine induced gene 1 AB032952 KIAA1126 KIAA1126 protein Hypothetical protein 102 4070 AB032965 CASKIN2 CASK interacting Hypothetical protein, ANK repeat, 103 4071 protein 2 Repeat AB032973 LCHN LCHN protein Hypothetical protein 104 4072 AB032976 P66 transcription Hypothetical protein 105 4073 repressor p66 beta component of the MeCP1 complex AB032993 GRIPAP1 GRIP1 associated Hypothetical protein 106 4074 protein 1 AB033009 KIAA1183 KIAA1183 protein Hypothetical protein 107 4075 AB033037 KIAA1211 KIAA1211 protein Hypothetical protein 108 4076 AB033050 RAI17 retinoic acid induced Hypothetical protein 109 4077 17 AB033053 ZNF295 zinc finger protein Transcription regulation, DNA- 110 4078 295 binding, Zinc-finger, Metal-binding, Nuclear protein, Repeat AB033055 KIAA1229 KIAA1229 protein Hypothetical protein 111 4079 AB033068 FZR1 Fzr1 protein Hypothetical protein, Ubl conjugation 112 4080 pathway, Cell cycle, Cell division, Mitosis, Repeat, WD repeat, Phosphorylation, Alternative splicing AB033070 KIAA1244 KIAA1244 Hypothetical protein 113 4081 AB033073 KIAA1247 sulfatase 2 Hydrolase, Signal, Glycoprotein, 114 4082 Endoplasmic reticulum, Golgi stack AB033085 KIAA1259 hypothetical protein Hypothetical protein, ATP-binding, 115 4083 KIAA1259 Helicase, Hydrolase AB033087 TLE4 transducin-like Transcription regulation, Repressor, 116 4084 enhancer of split 4 Nuclear protein, Repeat, WD repeat, (E(sp1) homolog, Phosphorylation, Wnt signaling Drosophila) pathway AB033091 KIAA1265 solute carrier family Hypothetical protein 117 4085 39 (zinc transporter), member 10 AB033092 MTA3 metastasis Hypothetical protein, Zinc-finger, 118 4086 associated family, Nuclear protein, Alternative splicing member 3 AB033100 KIAA1274 KIAA protein (similar Hypothetical protein 119 4087 to mouse paladin) AB033108 KCNH3 potassium voltage- Hypothetical protein, Transport, Ion 120 4088 gated channel, transport, Ionic channel, Voltage- subfamily H (eag- gated channel, Potassium channel, related), member 3 Potassium transport, Transmembrane, Glycoprotein, Multigene family AB033112 BRPF3 bromodomain and Hypothetical protein, Zinc-finger, 121 4089 PHD finger Bromodomain containing, 3 AB033118 ZDHHC8 zinc finger, DHHC Transmembrane, Zinc-finger, 122 4090 domain containing 8 Hypothetical protein AB037716 KIAA1295 KIAA1295 protein Hypothetical protein, SH3 domain 123 4091 AB037720 SH2B SH2-B homolog Hypothetical protein 124 4092 AB037721 STARD9 START domain Hypothetical protein 125 4093 containing 9 AB037722 KIAA1301 NEDD4-related E3 Hypothetical protein 126 4094 ubiquitin ligase NEDL2 AB037729 RALGDS ral guanine Guanine-nucleotide releasing factor, 127 4095 nucleotide 3D-structure, Hypothetical protein dissociation stimulator AB037749 KIAA1328 KIAA1328 protein Hypothetical protein 128 4096 AB037757 KIAA1336 WD repeat domain Hypothetical protein, Repeat, WD 129 4097 35 repeat AB037760 ZNF398 zinc finger protein Transcription regulation, Activator, 130 4098 398 DNA-binding, Zinc-finger, Metal- binding, Nuclear protein, Repeat, Alternative splicing AB037771 KIAA1350 ubiquitin specific Hypothetical protein 131 4099 protease 53 AB037787 NLGN2 neuroligin 2 Cell adhesion, Glycoprotein, Signal, 132 4100 Transmembrane AB037795 KIAA1374 KIAA1374 protein Hypothetical protein, Repeat, WD 133 4101 repeat AB037802 COG1 component of Transport, Protein transport, Golgi 134 4102 oligomeric golgi stack, Membrane complex 1 AB037813 DKFZp762K222 hypothetical protein Hypothetical protein 135 4103 DKFZp762K222 AB037814 KIAA1393 KIAA1393 Hypothetical protein 136 4104 AB037836 PRex1 phosphatidylinositol Guanine-nucleotide releasing factor, 137 4105 3,4,5-trisphosphate- Repeat, Alternative splicing dependent RAC exchanger 1 AB037845 ARHGAP10 Rho GTPase Hypothetical protein 138 4106 activating protein 21 AB037851 KIAA1430 KIAA1430 protein Hypothetical protein 139 4107 AB037855 KIAA1434 hypothetical protein Hypothetical protein 140 4108 KIAA1434 AB037859 MKL1 megakaryoblastic Transcription regulation, Nuclear 141 4109 leukemia protein, Coiled coil, Repeat, (translocation) 1 Chromosomal translocation, Protooncogene AB037860 NFIA nuclear factor I/A Activator, DNA replication, DNA- 142 4110 binding, Nuclear protein, Transcription, Transcription regulation, Multigene family AB037861 DKFZP586J0619 DKFZP586J0619 Hypothetical protein 143 4111 Protein AB040881 KIF1B kinesin family Hypothetical protein, Motor protein, 144 4112 member 1B Microtubule, ATP-binding, Coiled coil, Mitochondrion, Alternative splicing, Disease mutation, Charcot- Marie-Tooth disease AB040900 KIAA1467 KIAA1467 protein Hypothetical protein 145 4113 AB040907 KIAA1474 zinc finger protein Hypothetical protein, Metal-binding, 146 4114 537 Zinc, Zinc-finger AB040908 VPS18 vacuolar protein Transport, Protein transport, 147 4115 sorting protein 18 Membrane, Zinc-finger, Coiled coil, Alternative splicing AB040917 KIAA1484 leucine rich repeat Hypothetical protein, 148 4116 and fibronectin type Immunoglobulin domain III domain containing 1 AB040930 LRRN1 leucine rich repeat Hypothetical protein, 149 4117 neuronal 1 Immunoglobulin domain AB040942 KIAA1509 KIAA1509 Hypothetical protein, Plasmid 150 4118 AB040955 KIAA1522 KIAA1522 protein Hypothetical protein 151 4119 AB040960 FLJ22670 lymphocyte alpha- Hypothetical protein, Kinase 152 4120 kinase AB040961 DTX2 deltex homolog 2 Nuclear protein, Repeat, Metal- 153 4121 (Drosophila) binding, Zinc, Zinc-finger, Alternative splicing, Polymorphism AB040968 HCN3 hyperpolarization Transport, Ion transport, Ionic 154 4122 activated cyclic channel, Voltage-gated channel, nucleotide-gated Potassium channel, Potassium, potassium channel 3 Potassium transport, Sodium transport, cAMP, cAMP-binding, Transmembrane, Glycoprotein, Sodium channel AB040969 KIAA1536 KIAA1536 protein Hypothetical protein 155 4123 AB040972 FLJ11560 Homo sapiens Hypothetical protein 156 4124 mRNA for KIAA1539 protein, partial cds. AF000560 hypothetical protein Metal-binding, Zinc, Zinc-finger 157 4125 LOC126208 AF007217 TRIP11 thyroid hormone Antigen, Golgi stack, Coiled coil, 158 4126 receptor interactor Chromosomal translocation, 11 Hypothetical protein AF011757 S100A12 S100 calcium Calcium-binding, Zinc, Metal-binding 159 4127 binding protein A12 (calgranulin C) AF016267 TNFRSF10C tumor necrosis factor Receptor, Apoptosis, Glycoprotein, 160 4128 receptor superfamily, Repeat, GPI-anchor, Signal, member 10c, decoy Lipoprotein without an intracellular domain AF016495 AQP9 aquaporin 9 Transport, Repeat, Transmembrane 161 4129 AF017433 ZNF213 zinc finger protein Transcription regulation, DNA- 162 4130 213 binding, Zinc-finger, Metal-binding, Nuclear protein, Repeat AF026816 ITPA inosine Hydrolase, Nucleotide metabolism, 163 4131 triphosphatase Disease mutation (nucleoside triphosphate pyrophosphatase) AF031166 SRP46 Splicing factor, 164 4132 arginine/serine-rich, 46 kD AF034803 PPFIBP2 PTPRF interacting Receptor, Hypothetical protein 165 4133 protein, binding protein 2 (liprin beta 2) AF035307 plexin C1 166 4134 AF038193 ADP-ribosylation GTP-binding, Multigene family, 167 4135 factor-like 3 Polymorphism AF038535 SYT7 synaptotagmin VII Transmembrane, Repeat, Synapse 168 4136 AF038554 DENR density-regulated Hypothetical protein 169 4137 protein AF043469 NXPH4 serine Transferase, Methyltransferase, 170 4138 hydroxymethyltransferase 2 Pyridoxal phosphate, One-carbon (mitochondrial) metabolism, Mitochondrion, Transit peptide, Glycoprotein, Repeat, Signal, Hypothetical protein AF045229 RGS10 regulator of G- Signal transduction inhibitor, 171 4139 protein signalling 10 Lipoprotein, Palmitate, Alternative splicing, Polymorphism AF049140 UBE2V2 ubiquitin-conjugating Ligase, Ubl conjugation pathway, 172 4140 enzyme E2 variant 2 Vitamin D AF052093 NJMU-R1 protein kinase Njmu- 173 4141 R1 AF052117 chloride channel 4 Ionic channel, Ion transport, Chloride 174 4142 channel, Chloride, Voltage-gated channel, Transmembrane, CBS domain, Repeat AF052159 protein tyrosine 175 4143 phosphatase-like (proline instead of catalytic arginine), member b AF052167 MRS2L MRS2-like, Signal, Hypothetical protein 176 4144 magnesium homeostasis factor (S. cerevisiae) AF052169 LOC115207 potassium channel Hypothetical protein 177 4145 tetramerisation domain containing 12 AF052181 epimorphin 178 4146 AF055006 SEC6 SEC6-like 1 (S. cerevisiae) Hypothetical protein, Exocytosis, 179 4147 Transport, Protein transport, Coiled coil, Alternative splicing AF055012 TGIF2 TGFB-induced factor DNA-binding, Homeobox, 180 4148 2 (TALE family Transcription regulation, Nuclear homeobox) protein, Phosphorylation AF055016 C13orf1 chromosome 13 Hypothetical protein 181 4149 open reading frame 1 AF055019 homeodomain Transferase, Serine/threonine- 182 4150 interacting protein protein kinase, ATP-binding, Nuclear kinase 2 protein, Alternative splicing AF055029 hypothetical protein 183 4151 LOC151162 AF055270 SFRS7 Homo sapiens heat- Nuclear protein, RNA-binding, 184 4152 shock suppressed mRNA splicing, Alternative splicing, protein 1 (HSSG1) Phosphorylation, Repeat, Zinc- mRNA, complete finger, Hypothetical protein cds. AF059531 PRMT3 protein arginine N- Hypothetical protein, Transferase, 185 4153 methyltransferase 3 Methyltransferase, Zinc-finger AF062341 CTNND1 catenin (cadherin- Cytoskeleton, Structural protein, 186 4154 associated protein), Phosphorylation, Repeat, Cell delta 1 adhesion, Coiled coil, Nuclear protein, Alternative splicing AF063020 PSIP2 PC4 and SFRS1 Receptor 187 4155 interacting protein 1 AF067972 DNMT3A DNA (cytosine-5-)- Methyltransferase, Transferase, 188 4156 methyltransferase 3 Zinc-finger, Metal-binding, Nuclear alpha protein, Hypothetical protein AF068296 MRPS35 mitochondrial Hypothetical protein, Ribosomal 189 4157 ribosomal protein protein, Mitochondrion S35 AF070587 Clone 24741 mRNA 190 4158 sequence AF070643 LOC55977 intraflagellar 191 4159 transport protein IFT20 AF072810 BAZ1B bromodomain Transcription regulation, 192 4160 adjacent to zinc Bromodomain, Zinc-finger, Coiled finger domain, 1B coil, Nuclear protein, Alternative splicing, Williams-Beuren syndrome AF073519 SERF1A small EDRK-rich Alternative splicing 193 4161 factor 1A (telomeric) AF073931 CACNA1H calcium channel, Ionic channel, Transmembrane, Ion 194 4162 voltage-dependent, transport, Voltage-gated channel, alpha 1H subunit Calcium channel, Glycoprotein, Repeat, Multigene family, Calcium- binding, Phosphorylation, Alternative splicing AF077965 CLN3 ceroid-lipofuscinosis, Transmembrane, Lysosome, 195 4163 neuronal 3, juvenile Glycoprotein, Alternative splicing, (Batten, Spielmeyer- Neuronal ceroid lipofuscinosis, Vogt disease) Disease mutation AF078843 LOC51202 DEAD (Asp-Glu-Ala- ATP-binding, Helicase, Hydrolase, 196 4164 Asp) box polypeptide Hypothetical protein 47 AF085243 ZNF236 zinc finger protein Metal-binding, Nuclear protein, Zinc, 197 4165 236 Zinc-finger, Hypothetical protein, Transcription regulation, DNA- binding, Repeat, Alternative splicing AF090935 C20orf3 Homo sapiens clone Transmembrane, Signal-anchor, 198 4166 HQ0569. Glycoprotein, Polymorphism AF097021 GW112 differentially 199 4167 expressed in hematopoietic lineages AF112213 C20orf24 chromosome 20 Alternative splicing 200 4168 open reading frame 24 AF112219 ESD esterase Hydrolase, Serine esterase, 201 4169 D/formylglutathione Polymorphism hydrolase AF113694 NF2 neurofibromin 2 Structural protein, Cytoskeleton, 202 4170 (bilateral acoustic Anti-oncogene, Disease mutation, neuroma) Alternative splicing, Deafness, 3D- structure AF114264 nexilin nexilin (F actin Hypothetical protein 203 4171 binding protein) AF116238 PUS1 pseudoundylate Lyase, tRNA processing, Nuclear 204 4172 synthase 1 protein AF117236 MATR3 matrin 3 Nuclear protein, RNA-binding, 205 4173 Repeat, Zinc-finger AF119665 PP pyrophosphatase Hydrolase, Metal-binding, 206 4174 (inorganic) Magnesium AF119856 PRO1851 Homo sapiens Acute phase, Serine protease 207 4175 mRNA for PK-120, inhibitor, Repeat, Signal, Multigene complete cds. family, Glycoprotein, Alternative splicing, Polymorphism AF121856 SNX6 sorting nexin 6 Hypothetical protein, Transport, 208 4176 Protein transport AF126749 SCA8 SCA8 mRNA, repeat 209 4177 region AF127765 CAPN3 calpain 3, (p94) Hydrolase, Thiol protease, Calcium- 210 4178 binding, Multigene family, Repeat, Disease mutation, Polymorphism, Alternative splicing AF131760 LRP10 low density Hypothetical protein, Plasmid 211 4179 lipoprotein receptor- related protein 10 AF131764 MPP5 membrane protein, Hypothetical protein, SH3 domain, 212 4180 palmitoylated 5 Membrane (MAGUK p55 subfamily member 5) AF131768 FLJ13657 chromosome 9 open Hypothetical protein 213 4181 reading frame 82 AF131774 FLJ14800 hypothetical protein Hypothetical protein 214 4182 FLJ14800 AF131775 MGC5560 hypothetical protein Hypothetical protein 215 4183 MGC5560 AF131784 RAB27B, member GTP-binding, Lipoprotein, 216 4184 RAS oncogene Prenylation family AF131803 MGC5508 hypothetical protein Hypothetical protein 217 4185 MGC5508 AF131812 likely ortholog of Hypothetical protein 218 4186 mouse monocyte macrophage 19 AF131838 FLJ12806 hypothetical protein Hypothetical protein 219 4187 FLJ12806 AF131842 KIAA1857 netrin G2 Hypothetical protein, EGF-like 220 4188 domain, Laminin EGF-like domain, Neurogenesis, Glycoprotein, GPI- anchor, Membrane, Signal, Repeat, Lipoprotein AF131859 PA sulfide quinone Oxidoreductase, Flavoprotein, FAD, 221 4189 reductase-like NADP, Mitochondrion, Transit (yeast) peptide, Polymorphism AF134404 FADS3 fatty acid desaturase 3 Heme 222 4190 AF146277 CD2AP CD2-associated SH3 domain, SH3-binding, 223 4191 protein Phosphorylation, Coiled coil, Repeat AF152338 PCDHGC4 protocadherin Calcium, Calcium-binding, Cell 224 4192 gamma subfamily C, 3 adhesion, Glycoprotein, Transmembrane, Alternative splicing, Repeat, Signal, Multigene family AF152339 PCDHGC5 protocadherin Calcium, Calcium-binding, Cell 225 4193 gamma subfamily C, 3 adhesion, Glycoprotein, Transmembrane, Alternative splicing, Repeat, Signal, Multigene family AF155107 FLJ11806 nuclear protein Plasmid, Hypothetical protein 226 4194 UKp68 AF156603 WBSCR14 Williams Beuren Transcription regulation, Repressor, 227 4195 syndrome Nuclear protein, DNA-binding, chromosome region Williams-Beuren syndrome, 14 Alternative splicing AF161339 ARHGAP9 Rho GTPase Hypothetical protein, SH3 domain 228 4196 activating protein 9 AF161417 DKFZp564D177 nipsnap homolog 3A Hypothetical protein 229 4197 (C. elegans) AF161442 HSPC324 Similar to HSPC324 230 4198 (LOC389811), mRNA AF167706 CRIM1 cysteine-rich motor Signal 231 4199 neuron 1 AF187859 HSPBP1 hsp70-interacting Hypothetical protein 232 4200 protein AF202063 FGFR4 fibroblast growth ATP-binding, Immunoglobulin 233 4201 factor receptor 4 domain, Kinase, Receptor, Transferase, Tyrosine-protein kinase, Glycoprotein, Phosphorylation, Transmembrane, Repeat, Signal, Polymorphism, 3D- structure AF209931 7h3 hypothetical protein Hypothetical protein 234 4202 FLJ13511 AF212842 LILRA3 leukocyte Ig-like Receptor, Repeat, Signal, Immune 235 4203 receptor 9 response, Immunoglobulin domain, Glycoprotein, Antigen, Multigene family, Polymorphism AF217798 NDEL1 nudE nuclear Hypothetical protein 236 4204 distribution gene E homolog like 1 (A. nidulans) AF220417 LGTN ligatin Membrane, Alternative splicing 237 4205 AF222694 LGALS12 lectin, galactoside- Galectin, Lectin, Repeat, Nuclear 238 4206 binding, soluble, 12 protein, Alternative splicing (galectin 12) AF227924 SIGLEC9 sialic acid binding Ig- Cell adhesion, Lectin, Antigen, 239 4207 like lectin 9 Transmembrane, Signal, Glycoprotein, Immunoglobulin domain, Repeat, Polymorphism AF228704 GSR glutathione FAD, Flavoprotein, Oxidoreductase, 240 4208 reductase Redox-active center, NADP, Acetylation, Alternative initiation, Mitochondrion, Transit peptide, 3D- structure, Polymorphism AF232216 PIH1 Homo sapiens 241 4209 pregnancy-induced hypertension syndrome-related protein (PIH1) mRNA, partial cds. AF237413 RAP1GDS1 RAP1, GTP-GDP GTPase activation, Repeat, 242 4210 dissociation Alternative splicing stimulator 1 AF241831 HABP4 hyaluronan binding Hypothetical protein 243 4211 protein 4 AF242771 Mesenchymal stem 244 4212 cell protein DSC96 mRNA, partial cds AF244088 ZNF16 zinc finger protein 16 Hypothetical protein, Metal-binding, 245 4213 (KOX 9) Nuclear protein, Zinc, Zinc-finger, Transcription regulation, DNA- binding, Repeat AF246221 ITM2B integral membrane Hypothetical protein, 246 4214 protein 2B Transmembrane, Signal-anchor, Disease mutation, Amyloid, Deafness AF257175 PECI peroxisomal D3,D2- Isomerase, Peroxisome, 247 4215 enoyl-CoA Hypothetical protein isomerase AF260261 ABI-2 abl interactor 2 Kinase, SH3 domain 248 4216 AF272357 NPDC1 neural proliferation, Signal, Transmembrane, 249 4217 differentiation and Hypothetical protein control, 1 AI076473_RC rap2 interacting Hypothetical protein 250 4218 protein x AI282511_RC PTRF hypothetical protein Hypothetical protein 251 4219 FLJ10534 AI286310_RC HSPA5 qu91g07.x1 ATP-binding, Endoplasmic reticulum, 252 4220 NCI_CGAP_Gas4 Signal Homo sapiens cDNA clone IMAGE: 1979484 3′ similar to gb: M19645_cds1 78 KD GLUCOSE REGULATED PROTEIN PRECURSOR (HUMAN); mRNA sequence. AI339981_RC hypothetical protein 253 4221 LOC153346 AI347139_RC hypothetical protein 254 4222 MGC39372 AI355990_RC qy51g12.x1 255 4223 NCI_CGAP_Brn23 Homo sapiens cDNA clone IMAGE: 2015590 3′, mRNA sequence. AI434777_RC CDNA FLJ44280 fis, 256 4224 clone TRACH2001684 AI493593_RC th39c02.x1 257 4225 NCI_CGAP_Pan1 Homo sapiens cDNA clone IMAGE: 2120642 3′, mRNA sequence. AI668686_RC FLJ38281 hypothetical protein Hypothetical protein, Metal-binding, 258 4226 FLJ38281 Zinc, Zinc-finger AI677876_RC CDNA clone 259 4227 IMAGE: 4648334, partial cds AI695056_RC Sarcoma antigen 260 4228 NY-SAR-79 mRNA, partial cds AI928427_RC Transcribed 261 4229 sequences AJ000480 C8FW phosphoprotein ATP-binding, Receptor, Transferase 262 4230 regulated by mitogenic pathways AJ010228 RFPL1 ret finger protein-like 1 Zinc-finger, Metal-binding 263 4231 AJ010842 NTPBP XPA binding protein 1 GTP-binding 264 4232 AJ011414 plexin- plexin B1 Hypothetical protein, Receptor, 265 4233 B1/SEP Signal AJ133115 THG-1 TSC-22-like Hypothetical protein, Transcription 266 4234 regulation, Repressor, Nuclear protein AJ225028 GABBR1 gamma-aminobutyric Hypothetical protein, G-protein 267 4235 acid (GABA) B coupled receptor, Postsynaptic receptor, 1 membrane, Repeat, Signal, Transmembrane, Coiled coil, Sushi, Glycoprotein, Alternative splicing, Polymorphism, Receptor AJ243107 APAF1 Homo sapiens Apoptosis, ATP-binding, Repeat, 268 4236 mRNA for apoptotic WD repeat, Alternative splicing, 3D- protease activating structure factor-1 (Apaf-1 gene) (short form). AJ249377 IGHM immunoglobulin Immunoglobulin domain, 269 4237 lambda joining 3 Immunoglobulin C region, Glycoprotein, Repeat, Pyrrolidone carboxylic acid, Polymorphism, Membrane, Hypothetical protein, Receptor, T-cell, Signal AJ270996 TRPM5 transient receptor Ionic channel, Transmembrane 270 4238 potential cation channel, subfamily M, member 5 AJ271684 CLECSF5 C-type (calcium Transmembrane, Lectin 271 4239 dependent, carbohydrate- recognition domain) lectin, superfamily member 5 AJ272057 STRAIT11499 MID1 interacting Hypothetical protein 272 4240 G12-like protein AK000001 FLJ00001 chromosome 9 open Hypothetical protein 273 4241 reading frame 28 AK000004 FGD3 FGD1 family, 274 4242 member 3 AK000007 FLJ00007 hypothetical protein SH3 domain 275 4243 FLJ00007 AK000014 HYPE Huntingtin Hypothetical protein 276 4244 interacting protein E AK000035 FLJ22390 hypothetical protein Hypothetical protein 277 4245 FLJ22390 AK000168 KIAA1919 Homo sapiens cDNA Hypothetical protein 278 4246 FLJ20161 fis, clone COL09252, highly similar to L33930 Homo sapiens CD24 signal transducer mRNA. AK000175 hypothetical protein 279 4247 LOC93444 AK000212 FLJ10140 tRNA (5- Hypothetical protein, Transferase, 280 4248 methylaminomethyl- Methyltransferase, tRNA processing 2-thiouridylate)- methyltransferase 1 AK000216 FLJ20209 hypothetical protein 281 4249 FLJ20209 AK000242 RALGDS ral guanine Guanine-nucleotide releasing factor, 282 4250 nucleotide 3D-structure, Hypothetical protein dissociation stimulator AK000260 CDK5RAP3 Homo sapiens cDNA 283 4251 FLJ20253 fis, clone COLF6895. AK000354 KIAA1892 KIAA1892 Hypothetical protein, Repeat, WD 284 4252 repeat AK000425 FLJ25555 hypothetical protein Hypothetical protein 285 4253 FLJ25555 AK000435 LOC90987 zinc finger protein Hypothetical protein, Metal-binding, 286 4254 251 Nuclear protein, Zinc, Zinc-finger AK000539 DKFZP564K0822 hypothetical protein Hypothetical protein 287 4255 DKFZp564K0822 AK000552 WDR5 WD repeat domain 5 Hypothetical protein, WD repeat, 288 4256 Repeat AK000617 NFRKB hypothetical protein Hypothetical protein, Ligase, Ubl 289 4257 LOC92912 conjugation pathway AK000660 cyclin-dependent 290 4258 kinase 6 AK000684 FLJ22104 hypothetical protein Hypothetical protein 291 4259 FLJ22104 AK000689 CLONE24945 arrestin domain Hypothetical protein 292 4260 containing 2 AK000703 FLJ20696 hypothetical protein Hypothetical protein 293 4261 FLJ20696 AK000729 solute carrier family Hypothetical protein 294 4262 36 (proton/amino acid symporter), member 1 AK000757 BCL2L1 sortilin 1 Apoptosis, Mitochondrion, 295 4263 Alternative splicing, Transmembrane, 3D-structure AK000787 CDNA FLJ20780 fis, 296 4264 clone COL04256 AK000803 hypothetical protein 297 4265 LOC90624 AK000808 MGC4796 Ser/Thr-like kinase Hypothetical protein, ATP-binding, 298 4266 Kinase, Serine/threonine-protein kinase, Transferase AK000822 DKFZP564M182 DKFZP564M182 Hypothetical protein 299 4267 protein AK000824 TCTA T-cell leukemia 300 4268 translocation altered gene AK000838 KIAA1295 KIAA1295 protein Hypothetical protein 301 4269 AK000933 opsin 3 Photoreceptor, Retinal protein, 302 4270 (encephalopsin, Transmembrane, Lipoprotein, panopsin) Palmitate, G-protein coupled receptor, GTPase activation AK000939 hypothetical protein 303 4271 LOC286272 AK000967 3PAP phosphatidylinositol- Hypothetical protein 304 4272 3-phosphate associated protein AK001022 ISL2 ISL2 transcription Homeobox, DNA-binding, 305 4273 factor, Developmental protein, Nuclear LIM/homeodomain, protein, Repeat, LIM domain, Metal- (islet-2) binding, Zinc, Multigene family AK001036 MAD, mothers Transcription regulation, Multigene 306 4274 against family, Phosphorylation decapentaplegic homolog 5 (Drosophila) AK001069 UPF3A CDNA FLJ10207 fis, 307 4275 clone HEMBA1005475 AK001163 PAICS phosphoribosylaminoimidazole Multifunctional enzyme, Purine 308 4276 carboxylase, biosynthesis, Ligase, Lyase, phosphoribosylaminoimidazole Decarboxylase succinocarboxamide synthetase AK001166 FLJ11252 HBxAg Hypothetical protein 309 4277 transactivated protein 1 AK001228 chromosome 6 open 310 4278 reading frame 107 AK001319 C8FW phosphoprotein ATP-binding, Receptor, Transferase 311 4279 regulated by mitogenic pathways AK001362 ESDN endothelial and Hypothetical protein 312 4280 smooth muscle cell- derived neuropilin- like protein AK001394 hypothetical protein 313 4281 DKFZp762K222 AK001452 FLJ10839 Homo sapiens cDNA Hypothetical protein 314 4282 FLJ10590 fis, clone NT2RP2004392, weakly similar to MNN4 PROTEIN. AK001469 GNPNAT1 glucosamine- Hypothetical protein, Transferase 315 4283 phosphate N- acetyltransferase 1 AK001478 ARHU ras homolog gene GTP-binding, Lipoprotein, 316 4284 family, member U Prenylation AK001492 FLJ10637 hypothetical protein Hypothetical protein 317 4285 FLJ10637 AK001499 FLJ10637 hypothetical protein Hypothetical protein 318 4286 FLJ10637 AK001503 CDNA FLJ10641 fis, Metal-binding, Zinc, Zinc-finger 319 4287 clone NT2RP2005748 AK001526 DKFZp667B1218 hypothetical protein Hypothetical protein 320 4288 DKFZp667B1218 AK001536 Human full-length Plasmid 321 4289 cDNA 5-PRIME end of clone CS0DK007YB08 of HeLa cells of Homo sapiens (human) AK001539 TEM6 tensin-like SH2 Hypothetical protein 322 4290 domain containing 1 AK001565 AP3M1 adaptor-related Golgi stack, Protein transport, 323 4291 protein complex 3, Transport, Hypothetical protein mu 1 subunit AK001579 ARAP3 ARF-GAP, RHO- Hypothetical protein 324 4292 GAP, ankyrin repeat and plekstrin homology domains- containing protein 3 AK001612 hypothetical protein 325 4293 LOC90784 AK001630 ETS1 v-ets Proto-oncogene, Nuclear protein, 326 4294 erythroblastosis Transcription regulation, DNA- virus E26 oncogene binding, Phosphorylation, Alternative homolog 1 (avian) splicing, 3D-structure AK001731 MGC17943 hypothetical protein Hypothetical protein 327 4295 MGC17943 AK001758 THOC2 THO complex 2 Transport, mRNA transport, mRNA 328 4296 processing, mRNA splicing, Nuclear protein, RNA-binding, Alternative splicing AK001822 chromosome 9 open Hypothetical protein 329 4297 reading frame 37 AK001913 CL25084 XTP3-transactivated Hypothetical protein 330 4298 protein B AK001980 ADPRTL2 ADP- Transferase, Glycosyltransferase, 331 4299 ribosyltransferase NAD, DNA-binding, Nuclear protein, (NAD+; poly(ADP- Alternative splicing ribose) polymerase)- like 2 AK002039 MRVI1 murine retrovirus 332 4300 integration site 1 homolog AK002081 FLJ10287 hypothetical protein Hypothetical protein 333 4301 FLJ10287 AK002141 PIK4CA Homo sapiens cDNA Transferase, Kinase 334 4302 FLJ11279 fis, clone PLACE1009444, highly similar to PHOSPHATIDYLINOSITOL 4-KINASE ALPHA (EC 2.7.1.67). AK002146 hypothetical protein 335 4303 LOC153684 AK002174 KLHL5 kelch-like 5 Cytoskeleton, Actin-binding, Repeat, 336 4304 (Drosophila) Kelch repeat, Alternative splicing AL049232 Homo sapiens 337 4305 mRNA; cDNA DKFZp564P1816 (from clone DKFZp564P1816). AL049266 Homo sapiens 338 4306 mRNA; cDNA DKFZp564F093 (from clone DKFZp564F093). AL049279 MRNA; cDNA 339 4307 DKFZp564I083 (from clone DKFZp564I083) AL049299 DJ465N24.2.1 hypothetical protein Hypothetical protein 340 4308 dJ465N24.2.1 AL049309 SFRS12 splicing factor, Nuclear protein, mRNA processing, 341 4309 arginine/serine-rich mRNA splicing, Spliceosome, 12 Alternative splicing AL049365 FTL hypothetical protein Acetylation, Iron storage, Multigene 342 4310 MGC50853 family AL049381 pre-B-cell leukemia Transcription regulation, DNA- 343 4311 transcription factor 1 binding, Nuclear protein, Activator, Repressor, Homeobox, Proto- oncogene, Chromosomal translocation, Alternative splicing, Steroidogenesis, Sexual differentiation, 3D-structure AL049397 CGI-146 protein Hypothetical protein 344 4312 AL049415 ADAM19 a disintegrin and Hydrolase, Metalloprotease, Zinc, 345 4313 metalloproteinase Signal, Glycoprotein, Zymogen, domain 19 (meltrin Transmembrane, EGF-like domain, beta) SH3-binding, Alternative splicing, Hypothetical protein AL049431 FLJ20619 hypothetical protein Hypothetical protein 346 4314 FLJ20619 AL049450 hypothetical protein 347 4315 LOC339287 AL049471 AT rich interactive Hypothetical protein 348 4316 domain 5B (MRF1- like) AL049962 hypothetical protein 349 4317 LOC286148 AL049963 LOC64116 solute carrier family Hypothetical protein 350 4318 39 (zinc transporter), member 8 AL050002 hypothetical protein Hypothetical protein 351 4319 LOC169611 AL050021 solute carrier family Hypothetical protein, 352 4320 7 (cationic amino Transmembrane, Glycoprotein, acid transporter, y+ Transport, Amino-acid transport, system), member 1 Receptor AL050022 DKFZP564D116 DKFZP564D116 Hypothetical protein 353 4321 protein AL050050 TULIP1 GTPase activating Hypothetical protein 354 4322 RANGAP domain- like 2 pseudogene AL050060 DKFZP566H073 DKFZP566H073 Hypothetical protein, Metal-binding, 355 4323 protein Zinc, Zinc-finger AL050091 GRINL1A glutamate receptor, Hypothetical protein, Receptor 356 4324 ionotropic, N-methyl D-aspartate-like 1A AL050126 LAP1B lamina-associated Hypothetical protein 357 4325 polypeptide 1B AL050148 sorting nexin 1 Transport, Protein transport, Golgi 358 4326 stack, Alternative splicing AL050163 PIK3AP hematopoietic cell Hypothetical protein, 359 4327 signal transducer Transmembrane AL050164 CDYL chromodomain Hypothetical protein, Nuclear protein 360 4328 protein, Y-like AL050170 SLC26A6 solute carrier family Hypothetical protein, 361 4329 26, member 6 Transmembrane, Alternative splicing, Polymorphism AL050173 C21orf25 chromosome 21 Hypothetical protein 362 4330 open reading frame 25 AL050217 BRD2 dehydrogenase/reductase Oxidoreductase 363 4331 (SDR family) member 1 AL050346 C22orf3 chromosome 22 Hypothetical protein 364 4332 open reading frame 3 AL079294 MRNA full length Hypothetical protein 365 4333 insert cDNA clone EUROIMAGE 362780 AL079298 MCCC2 methylcrotonoyl- Mitochondrion, Transit peptide, 366 4334 Coenzyme A Ligase, Disease mutation, carboxylase 2 (beta) Alternative splicing AL080110 progestin and Hypothetical protein 367 4335 adipoQ receptor family member III AL080114 chromosome 10 Hypothetical protein 368 4336 open reading frame 72 AL080125 ZNF20 zinc finger protein 20 Hypothetical protein, Metal-binding, 369 4337 (KOX 13) Nuclear protein, Zinc, Zinc-finger, Transcription regulation, DNA- binding, Repeat AL080156 DKFZP434J214 TCDD-inducible Hypothetical protein 370 4338 poly(ADP-ribose) polymerase AL080169 DKFZP434C171 DKFZP434C171 Hypothetical protein 371 4339 protein AL080182 N-deacetylase/N- Hypothetical protein, Transferase, 372 4340 sulfotransferase Transmembrane, Glycoprotein, Golgi (heparan stack, Signal-anchor glucosaminyl) 2 AL080192 hypothetical protein Hypothetical protein 373 4341 LOC253782 AL096745 TBCD tubulin-specific Hypothetical protein 374 4342 chaperone d AL109669 IL16 interleukin 16 Cytokine, Chemotaxis, Repeat, 3D- 375 4343 (lymphocyte structure chemoattractant factor) AL109693 FLJ12587 hypothetical protein Hypothetical protein 376 4344 FLJ12587 AL109695 solute carrier organic Transmembrane, Transport, Ion 377 4345 anion transporter transport, Glycoprotein family, member 3A1 AL109699 MRNA full length Hypothetical protein 378 4346 insert cDNA clone EUROIMAGE 375854 AL109705 MRNA full length 379 4347 insert cDNA clone EUROIMAGE 73337 AL109786 WDR9 chromosome 21 Bromodomain, Repeat, WD repeat 380 4348 open reading frame 107 AL109817 FTCD formiminotransferase Hypothetical protein, Transferase, 381 4349 cyclodeaminase Lyase, Histidine metabolism, Multifunctional enzyme, Pyridoxal phosphate, Folate-binding, Alternative splicing, Disease mutation, Polymorphism AL110152 CD109 antigen (Gov Hypothetical protein 382 4350 platelet alloantigens) AL110188 ZNF10 zinc finger protein 10 Hypothetical protein, Metal-binding, 383 4351 (KOX 1) Nuclear protein, Zinc, Zinc-finger, Transcription regulation, DNA- binding, Repeat AL110200 Homo sapiens 384 4352 mRNA; cDNA DKFZp586B0922 (from clone DKFZp586B0922). AL110202 PORIMIN pro-oncosis receptor Hypothetical protein, Receptor, 385 4353 inducing membrane Transmembrane injury gene AL110210 PTPN23 protein tyrosine Hydrolase, Hypothetical protein, 386 4354 phosphatase, non- Receptor receptor type 23 AL110218 SLB selective LIM binding Hypothetical protein 387 4355 factor, rat homolog AL110238 RRN3 RNA polymerase I Initiation factor, Hypothetical protein 388 4356 transcription factor RRN3 AL110262 NCBP2 nuclear cap binding Transport, mRNA transport, Nuclear 389 4357 protein subunit 2, protein, RNA-binding, 3D-structure 20 kDa AL110277 KIAA0916 protein associated Hypothetical protein 390 4358 with Myc AL117415 ADAM33 Homo sapiens Hypothetical protein, Hydrolase, 391 4359 mRNA; cDNA Metalloprotease, Zinc, Signal, DKFZp434K0521 Glycoprotein, Zymogen, (from clone Transmembrane, EGE-like domain, DKFZp434K0521). Alternative splicing, Integrin, Protease AL117435 DKFZP434I216 DKFZP434I216 Hypothetical protein 392 4360 protein AL117448 RAB6IP1 RAB6 interacting Hypothetical protein 393 4361 protein 1 AL117452 FTHFSDC1 formyltetrahydrofolate Hypothetical protein 394 4362 synthetase domain containing 1 AL117457 CFL2 cofilin 2 (muscle) Nuclear protein, Actin-binding, 395 4363 Cytoskeleton, Phosphorylation, Alternative splicing AL117458 IHPK2 inositol Hypothetical protein, Kinase 396 4364 hexaphosphate kinase 2 AL117462 ZFP385 zinc finger protein Metal-binding, Zinc, Zinc-finger, 397 4365 385 Hypothetical protein AL117478 AGS3 G-protein signalling Hypothetical protein 398 4366 modulator 1 (AGS3- like, C. elegans) AL117519 hypothetical protein Hypothetical protein, Metal-binding, 399 4367 LOC152485 Zinc, Zinc-finger AL117573 DKFZP434F2021 DKFZP434F2021 Hypothetical protein 400 4368 protein AL117578 DKFZP434C128 chromosome 21 Hypothetical protein 401 4369 open reading frame 30 AL117609 DKFZp564O0463 DKFZP564O0463 Hypothetical protein, Repeat, WD 402 4370 protein repeat AL117639 FLJ12890 CCR4-NOT Hypothetical protein 403 4371 transcription complex, subunit 10 AL117643 activin A receptor, Receptor, Transferase, 404 4372 type IB Serine/threonine-protein kinase, ATP-binding, Transmembrane, Glycoprotein, Signal, Alternative splicing, Phosphorylation, Polymorphism AL117645 EG1 endothelial-derived Hypothetical protein 405 4373 gene 1 AL117654 ARH LDL receptor Hypothetical protein 406 4374 adaptor protein AL122053 TRIM3 tripartite motif- Zinc-finger, Coiled coil, Alternative 407 4375 containing 3 splicing AL122091 LOC56965 hypothetical protein Hypothetical protein 408 4376 from EUROIMAGE 1977056 AL122097 FLJ12519 hypothetical protein Hypothetical protein, Repeat, WD 409 4377 FLJ12519 repeat AL122098 NICAL NEDD9 interacting Hypothetical protein, LIM domain, 410 4378 protein with calponin Metal-binding, Zinc, Cytoskeleton homology and LIM domains AL122123 MRNA; cDNA 411 4379 DKFZp434M038 (from clone DKFZp434M038) AL133021 STAB2 stabilin 2 EGF-like domain, Laminin EGF-like 412 4380 domain, Hypothetical protein, Receptor AL133071 DKFZp434I1117 hypothetical protein Hypothetical protein 413 4381 DKFZp434I1117 AL133092 DKFZp434I0428 dispatched homolog Hypothetical protein 414 4382 1 (Drosophila) AL133094 PHF10 PHD finger protein Hypothetical protein 415 4383 10 AL133115 cytosolic ovarian Biological rhythms, Electron 416 4384 carcinoma antigen 1 transport, Growth regulation, Oxidoreductase, NAD, Membrane, Copper, Glycoprotein AL133116 FKBP10 Homo sapiens Isomerase, Rotamase, Endoplasmic 417 4385 mRNA; cDNA reticulum, Calcium-binding, DKFZp586I0821 Glycoprotein, Phosphorylation, (from clone Repeat, Signal, Hypothetical protein DKFZp586I0821). AL133117 THO complex 2 Transport, mRNA transport, mRNA 418 4386 processing, mRNA splicing, Nuclear protein, RNA-binding, Alternative splicing AL133426 AKAP13 A kinase (PRKA) Kinase, Receptor, cAMP, 419 4387 anchor protein 13 Hypothetical protein AL133572 DKFZp434I0535 Homo sapiens Hypothetical protein 420 4388 mRNA; cDNA DKFZp434I0535 (from clone DKFZp434I0535); partial cds. AL133577 MRNA; cDNA 421 4389 DKFZp434G0972 (from clone DKFZp434G0972) AL133580 SCOC short coiled-coil Hypothetical protein 422 4390 protein AL133581 FLJ25785 solute carrier family Hypothetical protein 423 4391 39 (zinc transporter), member 13 AL133592 MGC15548 zinc finger protein Hypothetical protein, Metal-binding, 424 4392 496 Zinc, Zinc-finger AL133622 KIAA0876 jumonji domain Hypothetical protein 425 4393 containing 2B AL133632 DKFZp434E1818 Similar to Hypothetical protein, Metal-binding, 426 4394 hypothetical protein Zinc, Zinc-finger (LOC389822), mRNA AL133645 hypothetical protein 427 4395 LOC90133 AL133662 KIAA0913 KIAA0913 protein Hypothetical protein 428 4396 AL136549 CYFIP2 cytoplasmic FMR1 Hypothetical protein 429 4397 interacting protein 2 AL137273 DKFZP434I0714 hypothetical protein Hypothetical protein 430 4398 DKFZP434I0714 AL137298 DNAJB6 MRNA; cDNA Chaperone, Alternative splicing 431 4399 DKFZp434N2116 (from clone DKFZp434N2116) AL137302 TEX27 testis expressed Hypothetical protein 432 4400 sequence 27 AL137397 FLJ21820 hypothetical protein Hypothetical protein 433 4401 FLJ21820 AL137421 RBM10 RNA binding motif Hypothetical protein, Metal-binding, 434 4402 protein 10 Zinc, Zinc-finger, RNA-binding, Nuclear protein, Repeat AL137423 GU2 DEAD (Asp-Glu-Ala- ATP-binding, Helicase, Hydrolase, 435 4403 Asp) box polypeptide Hypothetical protein 50 AL137431 WBSCR17 Williams-Beuren Transferase, Hypothetical protein 436 4404 syndrome chromosome region 17 AL137442 C20orf177 chromosome 20 Hypothetical protein 437 4405 open reading frame 177 AL137473 C20orf67 Homo sapiens Alternative splicing, Hypothetical 438 4406 mRNA; cDNA protein DKFZp434E1723 (from clone DKFZp434E1723); partial cds. AL137477 CDH24 cadherin-like 24 Hypothetical protein, Calcium, 439 4407 Calcium-binding, Cell adhesion, Glycoprotein, Transmembrane, Repeat, Signal, Multigene family, Alternative splicing, Plasmid AL137480 FNBP4 formin binding Hypothetical protein 440 4408 protein 4 AL137491 hypothetical protein 441 4409 LOC148696 AL137509 DKFZp761A052 hypothetical protein Hypothetical protein 442 4410 DKFZp761A052 AL137514 IHPK2 inositol Hypothetical protein, Kinase 443 4411 hexaphosphate kinase 2 AL137516 FLJ22059 zinc finger protein Hypothetical protein, Metal-binding, 444 4412 574 Zinc, Zinc-finger, Nuclear protein AL137557 KIAA1529 KIAA1529 Hypothetical protein 445 4413 AL137567 KIAA1238 KIAA1238 protein Hypothetical protein 446 4414 AL137579 SNX26 sorting nexin 26 Hypothetical protein, Transport, 447 4415 Protein transport AL137597 C20orf110 chromosome 20 448 4416 open reading frame 110 AL137615 MKNK2 MAP kinase- Hypothetical protein, ATP-binding, 449 4417 interacting Kinase, Serine/threonine-protein serine/threonine kinase, Transferase, Translation kinase 2 regulation, Phosphorylation, Alternative splicing AL137631 FBXW5 Homo sapiens Hypothetical protein, Repeat, WD 450 4418 mRNA; cDNA repeat DKFZp434B205 (from clone DKFZp434B205); partial cds. AL137639 KIAA0721 TSPY-like 4 Hypothetical protein 451 4419 AL137648 DKFZP434J1813 ER-resident protein Redox-active center, Hypothetical 452 4420 ERdj5 protein AL137655 Homo sapiens Hypothetical protein 453 4421 mRNA; cDNA DKFZp434B2016 (from clone DKFZp434B2016). AL137662 DKFZp434P086 hypothetical protein Hypothetical protein, ATP-binding, 454 4422 LOC340371 Transferase AL137663 FLJ21791 pleckstrin homology- Hypothetical protein 455 4423 like domain, family B, member 2 AL137665 TUBGCP6 tubulin, gamma Microtubule, Repeat, Alternative 456 4424 complex associated splicing protein 6 AL137667 MAPK8 Homo sapiens Transferase, Serine/threonine- 457 4425 mRNA; cDNA protein kinase, ATP-binding, DKFZp434B231 Phosphorylation, Alternative splicing (from clone DKFZp434B231). AL137707 LOC55901 TPTE and PTEN Signal 458 4426 homologous inositol lipid phosphatase pseudogene AL137727 C14orf9 chromosome 14 Hypothetical protein, 459 4427 open reading frame 9 Transmembrane, Alternative splicing AL137733 hypothetical protein Hypothetical protein 460 4428 LOC284701 AL137736 Rho guanine Hypothetical protein 461 4429 nucleotide exchange factor (GEF) 19 AL137764 LOC64744 hypothetical protein Hypothetical protein 462 4430 AL133206 AL157432 TERA chromosome 12 Hypothetical protein 463 4431 open reading frame 14 AL157449 LOC84687 protein phosphatase Hypothetical protein 464 4432 1, regulatory subunit 9B, spinophilin AL157454 FLJ21313 HCV NS3- Hypothetical protein 465 4433 transactivated protein 2 AL157455 Clone 466 4434 IMAGE: 5288750, mRNA AL157457 PP1628 PH domain- Hypothetical protein 467 4435 containing protein AL157465 FLJ20186 hypothetical protein Hypothetical protein 468 4436 FLJ20186 AL157480 SH3BP1 lectin, galactoside- GTPase activation, SH3-binding, 469 4437 binding, soluble, 1 Hypothetical protein, Galectin, (galectin 1) Lectin, Multigene family, Acetylation AL157484 MRNA; cDNA 470 4438 DKFZp762M127 (from clone DKFZp762M127) AL161960 FLJ21324 chromosome 21 Hypothetical protein 471 4439 open reading frame 97 AL161972 ICAM2 hypothetical protein 3D-structure, Cell 472 4440 FLJ11724 adhesion, Glycoprotein, Immunoglobulin domain, Repeat, Signal, Transmembrane AL161977 PCTK3 PCTAIRE protein Hypothetical protein, ATP-binding, 473 4441 kinase 3 Kinase, Serine/threonine-protein kinase, Transferase AL161983 hypothetical protein 474 4442 MGC39820 AL161994 HEI10 cyclin B1 interacting Ubl conjugation pathway, Ligase, 475 4443 protein 1 Nuclear protein, Metal-binding, Zinc, Coiled coil, Zinc-finger, Phosphorylation, Ubl conjugation AL162013 PLXNA1 Homo sapiens Hypothetical protein 476 4444 mRNA; cDNA DKFZp761P19121 (from clone DKFZp761P19121); partial cds. AL162039 MOB1, Mps One 477 4445 Binder kinase activator-like 1A (yeast) AL162062 LOC91010 formin-like 3 Hypothetical protein 478 4446 AL353934 MUS81 MUS81 Endonuclease, Hypothetical protein 479 4447 endonuclease homolog (yeast) AL353952 PI4KII phosphatidylinositol Hypothetical protein, Kinase 480 4448 4-kinase type II AL353953 FLJ13055 lipid phosphate Hypothetical protein 481 4449 phosphatase-related protein type 2 AL355708 NEO1 neogenin homolog 1 Cell adhesion, Repeat, Signal, 482 4450 (chicken) Transmembrane, Immunoglobulin domain, Glycoprotein, Alternative splicing AW190932_RC GPI xl66g09.x1 Gluconeogenesis, Glycolysis, 483 4451 NCI_CGAP_Pan1 Isomerase, Growth factor, Cytokine, Homo sapiens cDNA Disease mutation, 3D-structure, clone Hypothetical protein IMAGE: 2679712 3′, mRNA sequence. AW273216_RC ring finger protein Hypothetical protein, Metal-binding, 484 4452 149 Zinc, Zinc-finger AW419203_RC KIAA0601 amine oxidase Hypothetical protein 485 4453 (flavin containing) domain 2 AW673036_RC PPP1R3B hypothetical protein Hypothetical protein 486 4454 LOC286044 BE671663_RC EVIN2 epidermodysplasia Transmembrane, Hypothetical 487 4455 verruciformis 2 protein BE672528_RC cyclin-dependent 488 4456 kinase 6 Contig10037_RC hypothetical protein Hypothetical protein 489 4457 DKFZp667C165 Contig1007_RC LOC51754 hypothetical protein Hypothetical protein 490 4458 LOC283070 Contig10162_RC MGC14276 hypothetical protein Hypothetical protein 491 4459 MGC14276 Contig1030_RC FLJ00026 dedicator of Guanine-nucleotide releasing factor 492 4460 cytokinesis 8 Contig10363_RC MRF2 AT rich interactive Hypothetical protein 493 4461 domain 5B (MRF1- like) Contig10373_RC hypothetical protein Hypothetical protein 494 4462 MGC21854 Contig10418_RC Transcribed 495 4463 sequences Contig10429_RC DKFZp434H2111 hypothetical protein Hypothetical protein 496 4464 DKFZp434H2111 Contig10531_RC microtubule- Microtubule, Cytoskeleton, Repeat, 497 4465 associated protein Alternative splicing, Acetylation, tau Phosphorylation, Glycoprotein, Polymorphism, Disease mutation, Alzheimer's disease, 3D-structure, Hypothetical protein Contig1056_RC LOC57106 K562 cell-derived Hypothetical protein 498 4466 leucine-zipper-like protein 1 Contig1061_RC KIAA0924 protein Hypothetical protein, Metal-binding, 499 4467 Nuclear protein, Zinc, Zinc-finger Contig10629_RC PERQ1 PERQ amino acid Hypothetical protein 500 4468 rich, with GYF domain 1 Contig1063_RC TRIM33 Homo sapiens cDNA Hypothetical protein 501 4469 FLJ35131 fis, clone PLACE6008824. Contig10670_RC Transcribed 502 4470 sequences Contig10690_RC spleen tyrosine Transferase, Tyrosine-protein 503 4471 kinase kinase, ATP-binding, Phosphorylation, SH2 domain, Repeat, Alternative splicing, 3D- structure Contig10750_RC Transcribed 504 4472 sequences Contig10844_RC CDNA FLJ31150 fis, Hypothetical protein 505 4473 clone IMR322001534 Contig11012_RC leukocyte-derived Aminopeptidase 506 4474 arginine aminopeptidase Contig11075_RC NFASC neurofascin Cell adhesion, Repeat, Signal, 507 4475 Transmembrane, Immunoglobulin domain, Glycoprotein, Alternative splicing, Polymorphism, Hypothetical protein Contig11266_RC Transcribed 508 4476 sequence with moderate similarity to protein ref: NP_054848.1 (H. sapiens) PRO0478 protein [Homo sapiens] Contig112_RC NICE-4 NICE-4 protein Hypothetical protein 509 4477 Contig1146_RC LOC90550 chromosome 10 Hypothetical protein 510 4478 open reading frame 42 Contig11_RC hypothetical protein Hypothetical protein 511 4479 LOC90462 Contig12140_RC Transcribed 512 4480 sequences Contig12201_RC splicing factor, Nuclear protein, RNA-binding, 513 4481 arginine/serine-rich 5 mRNA splicing, Alternative splicing, Repeat, Phosphorylation, Polymorphism, Plasmid Contig12540_RC Transcribed 514 4482 sequences Contig12750_RC hypothetical protein Hypothetical protein 515 4483 LOC257106 Contig12755_RC GCN1L1 homeodomain Transferase, Serine/threonine- 516 4484 interacting protein protein kinase, ATP-binding, Nuclear kinase 2 protein, Alternative splicing Contig12820_RC FLJ21709 nucleotide-binding Hypothetical protein 517 4485 oligomerization domains 27 Contig12855 MAPK8IP2 MRNA; cDNA Kinase, SH3 domain, Alternative 518 4486 DKFZp434J0428 splicing (from clone DKFZp434J0428) Contig1295_RC MDS033 protein F25965 Transmembrane, Golgi stack, 519 4487 Endoplasmic reticulum Contig13165_RC B4GALT6 UDP- Transferase, Glycosyltransferase, 520 4488 Gal:betaGlcNAc Glycoprotein, Transmembrane, beta 1,4- Signal-anchor, Golgi stack, galactosyltransferase, Manganese, Magnesium, Calcium, polypeptide 6 Multigene family Contig13387_RC FLJ21458 hypothetical protein Hypothetical protein 521 4489 FLJ21458 Contig13480_RC Transcribed 522 4490 sequences Contig13510_RC zinc finger protein Hypothetical protein, Metal-binding, 523 4491 325 Nuclear protein, Zinc, Zinc-finger, Transcription regulation, DNA- binding, Repeat Contig13609_RC Transcribed 524 4492 sequences Contig13643_RC Transcribed 525 4493 sequences Contig1366_RC DC-TM4F2 tetraspanin similar to Hypothetical protein, 526 4494 TM4SF9 Transmembrane Contig13766_RC Transcribed 527 4495 sequences Contig1386_RC SEMA4B sema domain, Transmembrane, Immunoglobulin 528 4496 immunoglobulin domain, Multigene family, domain (Ig), Neurogenesis, Developmental transmembrane protein, Glycoprotein, Signal, domain (TM) and Polymorphism short cytoplasmic domain, (semaphorin) 4B Contig1389_RC ITPR1 mitogen-activated ATP-binding, Kinase, Transferase, 529 4497 protein kinase 9 Serine/threonine-protein kinase, Phosphorylation, Alternative splicing Contig14039_RC FOXE3 forkhead box E3 Transcription regulation, DNA- 530 4498 binding, Nuclear protein Contig1403_RC LBH likely ortholog of Hypothetical protein 531 4499 mouse limb-bud and heart gene Contig14172 vitelliform macular Iron storage, Iron, Metal-binding, 3D- 532 4500 dystrophy (Best structure, Transport, Ion transport, disease, bestrophin) Ionic channel, Chloride channel, Calcium, Alternative splicing, Disease mutation, Polymorphism, Vision, Transmembrane, Phosphorylation Contig14197_RC Transcribed 533 4501 sequences Contig1422_RC hypothetical protein Hypothetical protein 534 4502 FLJ38426 Contig14282_RC Transcribed 535 4503 sequences Contig14433_RC Transcribed 536 4504 sequences Contig1447_RC EFG1 mitochondrial Elongation factor, Protein 537 4505 elongation factor G1 biosynthesis, Mitochondrion, Transit peptide, GTP-binding Contig14520_RC Transcribed 538 4506 sequences Contig14555_RC Transcribed 539 4507 sequences Contig14581_RC Transcribed 540 4508 sequences Contig14625_RC FLJ22021 hypothetical protein Repeat, WD repeat 541 4509 FLJ22021 Contig1462_RC C11orf15 chromosome 11 Transmembrane 542 4510 open reading frame 15 Contig14658_RC zx08b09.s1 543 4511 Soares_total_fetus_Nb2HF8_9w Homo sapiens cDNA clone IMAGE: 785849 3′, mRNA sequence. Contig14720_RC Transcribed 544 4512 sequences Contig14797_RC Transcribed 545 4513 sequences Contig14899_RC LOC146853 LOC146853 546 4514 Contig1505_RC MGC4308 hypothetical protein 547 4515 MGC4308 Contig151_RC ELKS CDNA FLJ31750 fis, Hypothetical protein 548 4516 clone NT2RI2007406 Contig15267_RC Transcribed 549 4517 sequences Contig15281_RC Chediak-Higashi Protein transport, Transport, Repeat, 550 4518 syndrome 1 WD repeat, Disease mutation, Alternative splicing Contig1540_RC ACTB serine Transferase, Acyltransferase, 551 4519 palmitoyltransferase, Transmembrane, Pyridoxal long chain base phosphate, Endoplasmic reticulum subunit 2 Contig15580_RC LOC401124 552 4520 (LOC401124), mRNA Contig15607_RC Transcribed 553 4521 sequences Contig15635_RC Transcribed 554 4522 sequences Contig15647_RC Transcribed 555 4523 sequences Contig15674_RC Transcribed 556 4524 sequences Contig15898_RC Transcribed 557 4525 sequence with weak similarity to protein ref: NP_055301.1 (H. sapiens) neuronal thread protein [Homo sapiens] Contig16192_RC Transcribed 558 4526 sequence with moderate similarity to protein ref: NP_110386.1 (H. sapiens) nuclear receptor binding factor-2 [Homo sapiens] Contig1619_RC NAPB N-ethylmaleimide- Hypothetical protein 559 4527 sensitive factor attachment protein, beta Contig1620_RC PPP1R16A protein phosphatase ANK repeat, Repeat, Coiled coil, 560 4528 1, regulatory Lipoprotein, Prenylation, Membrane (inhibitor) subunit 16A Contig16217_RC Transcribed 561 4529 sequences Contig1632_RC MGC17921 chromosome 14 Alternative splicing 562 4530 open reading frame 31 Contig16376_RC DKFZP564B1162 hypothetical protein Hypothetical protein 563 4531 DKFZp564B1162 Contig16437_RC Transcribed 564 4532 sequences Contig16440_RC Transcribed 565 4533 sequences Contig16441_RC Transcribed 566 4534 sequences Contig16447_RC C16orf44 chromosome 16 Hypothetical protein 567 4535 open reading frame 44 Contig16530_RC Transcribed 568 4536 sequences Contig16736_RC Clone Hypothetical protein 569 4537 IMAGE: 5561763, mRNA Contig16772_RC Transcribed 570 4538 sequences Contig16786_RC Transcribed 571 4539 sequences Contig1682_RC RCP Rab coupling protein Hypothetical protein 572 4540 Contig16908_RC MGC42174 hypothetical protein Hypothetical protein 573 4541 MGC42174 Contig16931_RC YR-29 TGF beta-inducible Nuclear protein 574 4542 nuclear protein 1 Contig1699_RC FLJ12438 hypothetical protein Hypothetical protein 575 4543 FLJ12438 Contig17017_RC Transcribed 576 4544 sequences Contig17084_RC DEAD (Asp-Glu-Ala- ATP-binding, Helicase, Hydrolase, 577 4545 Asp) box polypeptide Hypothetical protein 31 Contig17109_RC Similar to Protein 578 4546 C20orf27 (LOC390690), mRNA Contig17356_RC hypothetical protein Hypothetical protein 579 4547 FLJ13611 Contig17607_RC Transcribed 580 4548 sequences Contig1789_RC LAGY homeodomain-only Hypothetical protein, DNA-binding, 581 4549 protein Homeobox, Nuclear protein Contig178_RC syntrophin, beta 2 Actin-binding, Cytoskeleton, 582 4550 (dystrophin- Microtubule, Calcium-binding, associated protein Calmodulin-binding, Membrane, A1, 59 kDa, basic Phosphorylation, Repeat, component 2) Polymorphism, Multigene family, Alternative splicing Contig17982_RC hypothetical protein Hypothetical protein 583 4551 FLJ14624 Contig1798_RC MOX2 antigen identified by Antigen, Neurone, T-cell, Signal, 584 4552 monoclonal antibody Transmembrane, Immunoglobulin MRC OX-2 domain, Glycoprotein, Alternative splicing Contig18246_RC oz78a12.x1 585 4553 Soares_senescent_fibroblasts_NbHSF Homo sapiens cDNA clone IMAGE: 1681438 3′, mRNA sequence. Contig18286_RC pellino 3 alpha Alternative splicing 586 4554 Contig18476_RC Homo sapiens, clone 587 4555 IMAGE: 4830091, mRNA. Contig18493_RC oj35b09.s1 588 4556 NCI_CGAP_Lu5 Homo sapiens cDNA clone IMAGE: 1500281 3′, mRNA sequence. Contig18504_RC OR52K3P olfactory receptor, Hypothetical protein 589 4557 family 52, subfamily K, member 3 pseudogene Contig19023_RC yf45a10.s2 Soares 590 4558 fetal liver spleen 1NFLS Homo sapiens cDNA clone IMAGE: 129786 3′, mRNA sequence. Contig19064_RC hypothetical protein 591 4559 LOC340351 Contig19127_RC FLJ31295 hypothetical protein Metal-binding, Zinc, Zinc-finger, 592 4560 FLJ31295 Hypothetical protein Contig19210_RC Transcribed 593 4561 sequences Contig1924_RC C20orf11 chromosome 20 Coiled coil 594 4562 open reading frame 11 Contig19333_RC Transcribed 595 4563 sequences Contig1951 GNPAT MRNA; cDNA Transferase, Acyltransferase, 596 4564 DKFZp686J23256 Peroxisome, Membrane, Rhizomelic (from clone chondrodysplasia punctata, Disease DKFZp686J23256) mutation Contig19700_RC Transcribed 597 4565 sequences Contig19715_RC Transcribed 598 4566 sequences Contig1990_RC LOC92799 hypothetical protein Repeat, WD repeat, Hypothetical 599 4567 BC007653 protein Contig19918_RC Transcribed 600 4568 sequences Contig1991_RC PGA5 pepsinogen 5, group Hydrolase, Aspartyl protease, 601 4569 I (pepsinogen A) Digestion, Zymogen, Signal, Phosphorylation, 3D-structure, Polymorphism Contig19931_RC Transcribed 602 4570 sequences Contig20370_RC Transcribed 603 4571 sequences Contig20391_RC Transcribed 604 4572 sequence with strong similarity to protein pir: EFHU1 (H. sapiens) EFHU1 translation elongation factor eEF-1 alpha-1 chain — human Contig20427_RC Transcribed 605 4573 sequences Contig20600_RC CDNA FLJ34654 fis, 606 4574 clone KIDNE2018294 Contig20617_RC CDNA FLJ34031 fis, 607 4575 clone FCBBF2003895 Contig20830_RC Homo sapiens cDNA 608 4576 FLJ13550 fis, clone PLACE1007111. Contig20843_RC Transcribed 609 4577 sequences Contig20864_RC FLJ22529 hypothetical protein Hypothetical protein 610 4578 FLJ22529 Contig20913_RC FLJ12785 hypothetical protein Hypothetical protein 611 4579 FLJ12785 Contig20979_RC hypothetical protein 612 4580 MGC35555 Contig21098_RC Msx-interacting-zinc Multigene family, Zinc-finger, 613 4581 finger Nuclear protein, DNA-binding, Metal- binding, Alternative splicing Contig21116_RC Transcribed 614 4582 sequences Contig21200_RC Transcribed 615 4583 sequences Contig21268_RC Similar to 616 4584 hypothetical protein FLJ35867 (LOC342357), mRNA Contig2143_RC KIAA1771 dedicator of Hypothetical protein, Guanine- 617 4585 cytokinesis 7 nucleotide releasing factor, Alternative splicing Contig21627_RC CDNA FLJ39637 fis, Hypothetical protein 618 4586 clone SMINT2003003 Contig21787_RC Transcribed 619 4587 sequences Contig2179_RC FLJ32452 hypothetical protein Hypothetical protein 620 4588 FLJ32452 Contig21839_RC ow70g11.s1 621 4589 Soares_fetal_liver_spleen_1NFLS_S1 Homo sapiens cDNA clone IMAGE: 1652228 3′, mRNA sequence. Contig21847_RC KSP37 Ksp37 protein 622 4590 Contig21891_RC FLJ13231 hypothetical protein Hypothetical protein 623 4591 FLJ13231 Contig21904 immunoglobulin 624 4592 superfamily, member 2 Contig21997_RC Transcribed 625 4593 sequences Contig22003_RC Transcribed 626 4594 sequences Contig22025_RC FLJ10111 v-akt murine Hypothetical protein, ATP-binding, 627 4595 thymoma viral Transferase, Serine/threonine- oncogene homolog 1 protein kinase, Phosphorylation, Nuclear protein, Kinase Contig22418_RC PTP4A3 protein tyrosine 628 4596 phosphatase type IVA, member 3 Contig22526_RC Transcribed 629 4597 sequences Contig22551_RC Transcribed 630 4598 sequences Contig2263_RC KIAA1949 KIAA1949 Hypothetical protein 631 4599 Contig22844_RC DKFZp434H2111 hypothetical protein Hypothetical protein 632 4600 DKFZp434H2111 Contig22901_RC AGENCOURT_6640943 633 4601 NIH_MGC_99 Homo sapiens cDNA clone IMAGE: 5434077 5′, mRNA sequence. Contig23240_RC hypothetical protein Hypothetical protein 634 4602 FLJ12525 Contig23263_RC NR5A1 Homo sapiens cDNA Receptor, Transcription regulation, 635 4603 FLJ33539 fis, clone DNA-binding, Nuclear protein, Zinc- BRAMY2007610, finger, Disease mutation, highly similar to Hypothetical protein STEROIDOGENIC FACTOR 1. Contig23280 lecithin-cholesterol Cholesterol metabolism, Lipid 636 4604 acyltransferase metabolism, Transferase, Acyltransferase, Signal, Glycoprotein, Polymorphism, Disease mutation Contig23299_RC P5 BTG3 associated Hypothetical protein 637 4605 nuclear protein Contig2339_RC FLJ21032 stearoyl-CoA Hypothetical protein 638 4606 desaturase 4 Contig23423_RC Transcribed 639 4607 sequences Contig23525_RC KIAA0140 similar to CG9643- Hypothetical protein 640 4608 PA Contig23547_RC Clone 641 4609 IMAGE: 5214442, mRNA Contig23593_RC Transcribed 642 4610 sequences Contig23604_RC carnitine O- Transferase, Acyltransferase, Fatty 643 4611 octanoyltransferase acid metabolism, Transport, Peroxisome Contig23667_RC WD repeat and Nuclear protein, DNA-binding, 644 4612 HMG-box DNA Repeat, WD repeat binding protein 1 Contig24090 CDNA FLJ37425 fis, 645 4613 clone BRAWH2001530 Contig24094_RC CDNA FLJ30598 fis, 646 4614 clone BRAWH2009263 Contig24098_RC glutamate receptor, Receptor, Signal, Transmembrane, 647 4615 ionotropic, N-methyl Postsynaptic membrane, Calcium, D-aspartate 2D Glycoprotein, Ionic channel, Magnesium Contig2429_RC FLJ40142 protein Hypothetical protein 648 4616 Contig24450_RC Transcribed 649 4617 sequences Contig24453_RC Transcribed 650 4618 sequences Contig24600_RC Transcribed 651 4619 sequences Contig25041_RC yx89b03.s1 Soares 652 4620 melanocyte 2NbHM Homo sapiens cDNA clone IMAGE: 268877 3′, mRNA sequence. Contig25058_RC Transcribed 653 4621 sequences Contig2505_RC GLTP glycolipid transfer Transport, Lipid transport, Repeat, 654 4622 protein Acetylation Contig25107_RC ferredoxin 1 Metal-binding, Iron-sulfur, Iron, 2Fe—2S, 655 4623 Electron transport, Mitochondrion, Transit peptide Contig25126_RC Transcribed 656 4624 sequences Contig2531_RC FLJ12484 hypothetical protein Hypothetical protein 657 4625 FLJ12484 Contig25332_RC GDF11 cytokine induced Nuclear protein, DNA-binding, 658 4626 protein 29 kDa Transcription, Transcription regulation, Translation regulation Contig25362_RC DKFZP566A1524 hypothetical protein Hypothetical protein 659 4627 DKFZp566A1524 Contig25429_RC Transcribed 660 4628 sequences Contig25435_RC FLJ10803 hypothetical protein Hypothetical protein 661 4629 FLJ10803 Contig2544 FLJ11526 hypothetical protein Hypothetical protein 662 4630 FLJ11526 Contig25546_RC CCT6A itchy homolog E3 Ubl conjugation pathway, Ligase, 663 4631 ubiquitin protein Nuclear protein, Repeat, ligase (mouse) Phosphorylation, Alternative splicing Contig25595_RC KIAA1618 KIAA1618 Hypothetical protein 664 4632 Contig256 PSMD11 wt73b11.x1 Proteasome 665 4633 Soares_thymus_NHFTh Homo sapiens cDNA clone IMAGE: 2513085 3′ similar to TR: Q26195 Q26195 PVA1 GENE.; mRNA sequence. Contig25610_RC CDNA FLJ31796 fis, 666 4634 clone NT2RI2008841 Contig25744_RC Transcribed 667 4635 sequences Contig2576_RC DKFZP564O1664 hypothetical protein Hypothetical protein 668 4636 DKFZp564O1664 Contig25770_RC Clone 669 4637 IMAGE: 4817413, mRNA Contig25783_RC Clone 670 4638 IMAGE: 5555626, mRNA Contig2578_RC ORF1-FL49 putative nuclear Nuclear protein 671 4639 protein ORF1-FL49 Contig25827_RC FLJ13848 hypothetical protein Hypothetical protein 672 4640 FLJ13848 Contig2584_RC ribonuclease P Hydrolase, Nuclear protein, tRNA 673 4641 (14 kD) processing Contig25861_RC Transcribed 674 4642 sequences Contig25960_RC DKFZP564B0769 chromosome 6 open Hypothetical protein 675 4643 reading frame 111 Contig26014_RC SYTL3 synaptotagmin-like 3 676 4644 Contig26019_RC methionyl Aminopeptidase, Hypothetical 677 4645 aminopeptidase 2 protein, Hydrolase, Cobalt, 3D- structure Contig26059_RC Transcribed 678 4646 sequences Contig2608 SLC2A4RG SLC2A4 regulator Transcription regulation, DNA- 679 4647 binding, Nuclear protein, Zinc-finger, Metal-binding, Alternative splicing Contig26170_RC Transcribed 680 4648 sequences Contig26332_RC Transcribed 681 4649 sequences Contig263_RC MGC12435 chromosome 14 682 4650 open reading frame 168 Contig26405_RC TSLL2 immunoglobulin Immunoglobulin domain 683 4651 superfamily, member 4C Contig26416_RC Transcribed 684 4652 sequences Contig26461_RC Transcribed 685 4653 sequences Contig2647_RC BCAT1 branched chain Transferase, Aminotransferase, 686 4654 aminotransferase 1, Hypothetical protein, Branched-chain cytosolic amino acid biosynthesis, Pyridoxal phosphate Contig2648_RC MGC15407 similar to RIKEN 687 4655 cDNA 4931428D14 gene Contig2657_RC MGC16207 hypothetical protein Hypothetical protein 688 4656 MGC16207 Contig26622_RC BIC BIC transcript 689 4657 Contig26706_RC CDNA FLJ43676 fis, 690 4658 clone SYNOV4009129 Contig26998_RC WD repeat domain 1 Repeat, WD repeat, Actin-binding, 691 4659 Cytoskeleton, Alternative splicing, Polymorphism, Hypothetical protein Contig27060_RC Transcribed 692 4660 sequence with moderate similarity to protein pdb: 1LBG (E. coli) B Chain B, Lactose Operon Repressor Bound To 21-Base Pair Symmetric Operator Dna, Alpha Carbons Only Contig27084_RC CDNA FLJ45493 fis, 693 4661 clone BRTHA2008598 Contig27124_RC CDNA FLJ42250 fis, 694 4662 clone TKIDN2007828 Contig27145_RC Transcribed 695 4663 sequences Contig27228_RC amyloid beta (A4) Hypothetical protein 696 4664 precursor protein- binding, family B, member 1 interacting protein Contig2728_RC zinc finger protein Hypothetical protein, Metal-binding, 697 4665 596 Zinc, Zinc-finger Contig27338_RC Transcribed 698 4666 sequences Contig27386_RC C7orf13 chromosome 7 open 699 4667 reading frame 13 Contig27542_RC Transcribed 700 4668 sequences Contig27558_RC FLJ13163 MRNA; cDNA Hypothetical protein, Kinase 701 4669 DKFZp779J2459 (from clone DKFZp779J2459) Contig27725_RC Transcribed 702 4670 sequences Contig27765_RC potassium inwardly- Hypothetical protein, Ionic channel, 703 4671 rectifying channel, Ion transport, Voltage-gated subfamily J, member channel, Transmembrane, 15 Potassium transport Contig27776_RC hypothetical protein Hypothetical protein 704 4672 FLJ21106 Contig27797_RC DnaJ (Hsp40) Chaperone, Repeat, Zinc, Metal- 705 4673 homolog, subfamily binding, Prenylation, Lipoprotein, A, member 2 Membrane, Multigene family Contig27820_RC Transcribed 706 4674 sequences Contig27837_RC Transcribed 707 4675 sequence with weak similarity to protein ref: NP_060265.1 (H. sapiens) hypothetical protein FLJ20378 [Homo sapiens] Contig27896_RC HSPC009 protein 708 4676 Contig27915_RC MGC40042 hypothetical protein Hypothetical protein 709 4677 MGC40042 Contig27977_RC Transcribed 710 4678 sequences Contig28024_RC KIAA0955 caspase recruitment Apoptosis, Nuclear protein, 711 4679 domain family, Alternative splicing, Hypothetical member 8 protein Contig28050_RC Homo sapiens cDNA 712 4680 FLJ35764 fis, clone TESTI2004906, weakly similar to H. sapiens mRNA for SIRP-beta1. Contig2811_RC C8orf2 Homo sapiens Transmembrane, Alternative splicing 713 4681 mRNA; cDNA DKFZp667H242 (from clone DKFZp667H242); complete cds. Contig28164_RC Transcribed 714 4682 sequences Contig28181_RC ns17h07.s1 715 4683 NCI_CGAP_GCB1 Homo sapiens cDNA clone IMAGE: 1183933 3′, mRNA sequence. Contig28229_RC Transcribed 716 4684 sequences Contig2823_RC FLJ23499 chromosome 11 Hypothetical protein 717 4685 open reading frame 1 Contig28286_RC Transcribed 718 4686 sequences Contig28298_RC NUP62 UI-H-Bl0p-abm-b- Nuclear protein, Transport, 719 4687 04-0-UI.s1 Glycoprotein, Coiled coil, Repeat, NCI_CGAP_Sub2 Polymorphism Homo sapiens cDNA clone IMAGE: 2712150 3′, mRNA sequence. Contig28522_RC Clone 24653 mRNA 720 4688 sequence Contig28567_RC Transcribed 721 4689 sequences Contig2857_RC DKFZp761G2113 hypothetical protein Hypothetical protein 722 4690 DKFZp761G2113 Contig28707_RC ADAMTS13 a disintegrin-like and Protease, Hypothetical protein, 723 4691 metalloprotease Signal (reprolysin type) with thrombospondin type 1 motif, 13 Contig28760_RC cyclin-dependent 724 4692 kinase 6 Contig28766_RC Transcribed 725 4693 sequences Contig28787_RC hypothetical protein Hypothetical protein 726 4694 LOC120526 Contig2883_RC RALY Clone Ribonucleoprotein, RNA-binding, 727 4695 IMAGE: 5285100, Nuclear protein, Antigen, Alternative mRNA splicing, Polymorphism Contig28947_RC CDC25A cell division cycle Cell division, Mitosis, Hydrolase, 728 4696 25A Alternative splicing, Multigene family, 3D-structure, Hypothetical protein Contig28949 Clone 729 4697 IMAGE: 5268292, mRNA Contig28996_RC NHL repeat 730 4698 containing 1 Contig29171_RC CDNA FLJ11544 fis, 731 4699 clone HEMBA1002826 Contig29207_RC chromosome 20 732 4700 open reading frame 78 Contig29284_RC Transcribed 733 4701 sequences Contig292_RC FLJ22386 leucine zipper Hypothetical protein 734 4702 domain protein Contig2930_RC DAB2 CDNA FLJ35517 fis, Alternative splicing, Phosphorylation 735 4703 clone SPLEN2000698 Contig29349_RC Transcribed 736 4704 sequences Contig29362_RC hypothetical protein Hypothetical protein 737 4705 LOC338692 Contig29373_RC 24b2/STAC2 protein 738 4706 Contig29569_RC hypothetical protein Hypothetical protein 739 4707 MGC29898 Contig29732_RC hypothetical protein 740 4708 LOC338758 Contig29749_RC LOC85028 PNAS-123 741 4709 Contig29780_RC Transcribed 742 4710 sequences Contig29802_RC programmed cell Calcium-binding, Repeat, Apoptosis 743 4711 death 6 Contig29860_RC NFAM1 NFAT activation Hypothetical protein, Signal, 744 4712 molecule 1 Transmembrane, Immunoglobulin domain, Phosphorylation Contig2986_RC EEG1 C1q domain Hypothetical protein 745 4713 containing 1 Contig29887_RC DKFZp434J0617 hypothetical protein Hypothetical protein 746 4714 DKFZp434J0617 Contig29890_RC FLJ32449 ankyrin repeat Hypothetical protein, ANK repeat, 747 4715 domain 23 Repeat Contig29901_RC proteasome Proteasome, Hydrolase, Protease, 748 4716 (prosome, Acetylation, Alternative splicing, macropain) subunit, Phosphorylation, Threonine protease alpha type, 3 Contig29921_RC FLJ22570 Dok-like protein Hypothetical protein 749 4717 Contig29940_RC CMYA1 cardiomyopathy Hypothetical protein 750 4718 associated 1 Contig29954_RC CATSPER2 Clone 751 4719 IMAGE: 5294645, mRNA Contig29955_RC zj86d08.s1 752 4720 Soares_fetal_liver_spleen_1NFLS_S1 Homo sapiens cDNA clone IMAGE: 461775 3′, mRNA sequence. Contig29995_RC Transcribed 753 4721 sequences Contig30052_RC C18B11 C18B11 homolog Hypothetical protein 754 4722 (44.9 kD) Contig30109_RC PRKWNK4 protein kinase, lysine Hypothetical protein, ATP-binding, 755 4723 deficient 4 Transferase, Kinase, Serine/threonine-protein kinase Contig30154_RC Transcribed 756 4724 sequence with moderate similarity to protein sp: P39194 (H. sapiens) ALU7_HUMAN Alu subfamily SQ sequence contamination warning entry Contig3015_RC pleckstrin homology 757 4725 domain containing, family A (phosphoinositide binding specific) member 2 Contig30209_RC FLJ12649 hypothetical protein Hypothetical protein 758 4726 FLJ12649 Contig30378_RC FLJ10178 hypothetical protein Hypothetical protein 759 4727 FLJ10178 Contig30474_RC VIT vitrin Hypothetical protein 760 4728 Contig30484_RC Transcribed 761 4729 sequences Contig30496_RC ZNF219 LOC400176 Transcription regulation, DNA- 762 4730 (LOC387957), binding, Zinc-finger, Metal-binding, mRNA Nuclear protein, Repeat Contig30736_RC Transcribed 763 4731 sequences Contig30811_RC PRKRA MRNA; cDNA Kinase 764 4732 DKFZp686G1498 (from clone DKFZp686G1498) Contig30840_RC LOC63929 hypothetical protein Hypothetical protein 765 4733 LOC63929 Contig30934_RC MGC33993 hypothetical protein Hypothetical protein, Metal-binding, 766 4734 MGC33993 Zinc, Zinc-finger Contig3094_RC PINK1 PTEN induced Hypothetical protein, ATP-binding, 767 4735 putative kinase 1 Kinase, Serine/threonine-protein kinase, Transferase Contig30977_RC hypothetical protein 768 4736 LOC154790 Contig30989_RC MGC10744 hypothetical protein Hypothetical protein 769 4737 MGC10744 Contig31057_RC Transcribed 770 4738 sequences Contig31186_RC HNRPDL heterogeneous Nucleocapsid, Ribonucleoprotein 771 4739 nuclear ribonucleoprotein D- like Contig31361_RC dedicator of Hypothetical protein, Guanine- 772 4740 cytokinesis 7 nucleotide releasing factor, Alternative splicing Contig31366_RC LNPEP hypothetical protein Hypothetical protein 773 4741 FLJ39485 Contig31421_RC thyroid hormone Proteasome, Ubl conjugation 774 4742 receptor interactor pathway, Ligase 12 Contig31449_RC Transcribed 775 4743 sequence with weak similarity to protein sp: P39195 (H. sapiens) ALU8_HUMAN Alu subfamily SX sequence contamination warning entry Contig3147_RC MUM2 trafficking protein Transport, Endoplasmic reticulum, 776 4744 particle complex 1 Golgi stack, Disease mutation Contig31482_RC Transcribed 777 4745 sequences Contig31495 thyroid hormone Antigen, Golgi stack, Coiled coil, 778 4746 receptor interactor Chromosomal translocation, 11 Hypothetical protein Contig31513_RC Transcribed 779 4747 sequences Contig31525_RC Transcribed 780 4748 sequence with weak similarity to protein ref: NP_079364.1 (H. sapiens) hypothetical protein FLJ13241 [Homo sapiens] Contig31587_RC Human full-length Plasmid 781 4749 cDNA 5-PRIME end of clone CS0DK007YB08 of HeLa cells of Homo sapiens (human) Contig31597_RC PDE4DIP chromosome 1 Hypothetical protein 782 4750 amplified sequence 3 Contig31661_RC hypothetical protein Hypothetical protein, Repeat, WD 783 4751 FLJ10385 repeat Contig31664_RC MGC26979 hypothetical protein Hypothetical protein 784 4752 MGC26979 Contig31699_RC CDNA FLJ27273 fis, 785 4753 clone TMS00761 Contig31740_RC PFN1 hypothetical protein Metal-binding, Zinc, Zinc-finger, 786 4754 LOC285345 Transcription regulation, DNA- binding, Nuclear protein, Repeat Contig31864_RC FERM domain Hypothetical protein 787 4755 containing 3 Contig31906_RC similar to Hypothetical protein 788 4756 hypothetical protein FLJ13659 Contig31911_RC hypothetical protein Hypothetical protein 789 4757 LOC349136 Contig32027_RC CDNA FLJ46867 fis, 790 4758 clone UTERU3012293, weakly similar to Homo sapiens zinc finger protein 14 (KOX 6) (ZNF14) Contig32059_RC MGC17919 zinc finger and BTB Zinc, Hypothetical protein, Metal- 791 4759 domain containing 8 binding, Zinc-finger Contig32081_RC Full length insert 792 4760 cDNA clone YP77A07 Contig32103_RC Clone 793 4761 IMAGE: 4689481, mRNA Contig32123_RC Similar to ataxin 2 794 4762 binding protein 1 isoform gamma; hexaribonucleotide binding protein 1 (LOC339162), mRNA Contig32185_RC intimal thickness- 795 4763 related receptor Contig3228_RC VMP1 hypothetical protein Hypothetical protein 796 4764 LOC283680 Contig32322_RC quaking homolog, Hypothetical protein 797 4765 KH domain RNA binding (mouse) Contig32323_RC hypothetical protein Hypothetical protein 798 4766 FLJ13105 Contig32335_RC Transcribed 799 4767 sequences Contig32377_RC ubiquitin specific Protease 800 4768 protease 51 Contig32431_RC Transcribed 801 4769 sequences Contig3250_RC LOC92399 mitochondrial Hypothetical protein 802 4770 ribosome recycling factor Contig32540_RC Transcribed 803 4771 sequences Contig32550_RC ZFP93 zinc finger protein Transcription regulation, DNA- 804 4772 235 binding, Zinc-finger, Metal-binding, Nuclear protein, Repeat Contig32637_RC RAB27A, member GTP-binding, Lipoprotein, 805 4773 RAS oncogene Prenylation, Alternative splicing, family Disease mutation Contig32757 FLJ21069 hypothetical protein Hypothetical protein, ANK repeat, 806 4774 FLJ21069 Repeat Contig32825_RC polymerase (RNA) III 807 4775 (DNA directed) (32 kD) Contig32920 FUBP1 nexilin (F actin Hypothetical protein 808 4776 binding protein) Contig33062_RC chromosome 17 Hypothetical protein 809 4777 open reading frame 31 Contig3311_RC MGC13186 hypothetical protein Hypothetical protein, ATP-binding 810 4778 MGC13186 Contig33127_RC Sequence 161 from 811 4779 Patent WO0220754. Contig3313 FLJ23153 likely ortholog of Hypothetical protein 812 4780 mouse tumor necrosis-alpha- induced adipose- related protein Contig33188_RC Transcribed 813 4781 sequences Contig33207_RC Transcribed 814 4782 sequences Contig33224_RC Transcribed 815 4783 sequences Contig33273_RC chromodomain DNA-binding, Helicase, Hypothetical 816 4784 helicase DNA protein, ATP-binding, Hydrolase binding protein 1-like Contig3331_RC MKI67IP MKI67 (FHA 817 4785 domain) interacting nucleolar phosphoprotein Contig33334_RC Transcribed 818 4786 sequences Contig33369_RC Transcribed 819 4787 sequence with weak similarity to protein ref: NP_062553.1 (H. sapiens) hypothetical protein FLJ11267 [Homo sapiens] Contig33394_RC FLJ37318 ubiquitin specific Hypothetical protein 820 4788 protease 54 Contig3344 MGC2835 DEAD (Asp-Glu-Ala- ATP-binding, Helicase, Hydrolase, 821 4789 Asp) box polypeptide Hypothetical protein 54 Contig33442_RC MOB1, Mps One Hypothetical protein 822 4790 Binder kinase activator-like 2A (yeast) Contig33464_RC Similar to bA304I5.1 823 4791 (novel lipase) (LOC340654), mRNA Contig33540_RC SEMA3F ob92d09.s1 Signal, Immunoglobulin domain, 824 4792 NCI_CGAP_GCB1 Multigene family, Glycoprotein, Homo sapiens cDNA Polymorphism clone IMAGE: 1338833 3′, mRNA sequence. Contig33574_RC Transcribed 825 4793 sequences Contig3359_RC neuralized-like Hypothetical protein 826 4794 (Drosophila) Contig33703_RC FLJ21438 hypothetical protein Hypothetical protein 827 4795 FLJ21438 Contig33741_RC FLJ12428 DEP domain Hypothetical protein 828 4796 containing 6 Contig33760_RC chromosome 9 open 829 4797 reading frame 71 Contig33790_RC jun dimerization DNA-binding, Nuclear protein 830 4798 protein 2 Contig33810_RC FLJ31528 hypothetical protein Hypothetical protein 831 4799 FLJ31528 Contig33831_RC Transcribed 832 4800 sequences Contig33852_RC OPRL1 opiate receptor-like 1 G-protein coupled receptor, 833 4801 Transmembrane, Glycoprotein, Phosphorylation, Lipoprotein, Palmitate, Alternative splicing Contig33888_RC ow44c09.x1 834 4802 Soares_parathyroid_tumor_NbHPA Homo sapiens cDNA clone IMAGE: 1649680 3′, mRNA sequence. Contig3390_RC FLJ12619 chromosome 6 open Hypothetical protein 835 4803 reading frame 62 Contig33951_RC nuclear pore Nuclear protein, Transport 836 4804 complex protein Contig33967_RC Transcribed 837 4805 sequences Contig33987 hypothetical protein Hypothetical protein 838 4806 KIAA1109 Contig33996_RC Transcribed 839 4807 sequences Contig34019_RC MGC15827 hypothetical protein Hypothetical protein 840 4808 MGC15827 Contig34051_RC Transcribed 841 4809 sequences Contig34090_RC Transcribed 842 4810 sequences Contig340_RC PPP1R15B protein phosphatase Hypothetical protein 843 4811 1, regulatory (inhibitor) subunit 15B Contig34118_RC Transcribed 844 4812 sequences Contig34231_RC yd77f12.s1 Soares 845 4813 fetal liver spleen 1NFLS Homo sapiens cDNA clone IMAGE: 114287 3′, mRNA sequence. Contig34286_RC Transcribed 846 4814 sequences Contig34291_RC nuclear receptor Transcription regulation, Receptor, 847 4815 subfamily 3, group Trans-acting factor, Nuclear protein, C, member 1 DNA-binding, Steroid-binding, Zinc- (glucocorticoid finger, Phosphorylation, Ubl receptor) conjugation, Alternative initiation, Alternative splicing, Polymorphism, Disease mutation Contig34302_RC hypothetical protein 848 4816 LOC150166 Contig34303_RC SFXN5 sideroflexin 5 Transport, Iron transport, Iron, 849 4817 Mitochondrion, Transmembrane Contig34350_RC CDNA FLJ45384 fis, 850 4818 clone BRHIP3021987 Contig34470_RC similar to kinesin Hypothetical protein 851 4819 family member 21A; N-5 kinesin Contig34554_RC CDNA FLJ33367 fis, 852 4820 clone BRACE2005661 Contig34593_RC Transcribed 853 4821 sequences Contig34607_RC ym49g02.s1 Soares 854 4822 infant brain 1NIB Homo sapiens cDNA clone IMAGE: 51586 3′, mRNA sequence. Contig34634_RC GCN1L1 homeodomain Transferase, Serine/threonine- 855 4823 interacting protein protein kinase, ATP-binding, Nuclear kinase 2 protein, Alternative splicing Contig34672_RC Transcribed 856 4824 sequences Contig3474_RC CDNA: FLJ22541 857 4825 fis, clone HSI00130 Contig34768_RC chromosome 21 Hypothetical protein 858 4826 open reading frame 59 Contig34779_RC SH3-domain kinase SH3 domain, Repeat, Membrane, 859 4827 binding protein 1 Nuclear protein, Coiled coil, Polymorphism, Alternative splicing Contig34880_RC Transcribed 860 4828 sequences Contig3495_RC MGC45416 hypothetical protein Hypothetical protein 861 4829 MGC45416 Contig34983_RC Transcribed 862 4830 sequences Contig34998_RC TMLHE CDNA FLJ25895 fis, Hypothetical protein 863 4831 clone CBR03553 Contig34999_RC periplakin Keratinization, Repeat, Coiled coil, 864 4832 Cytoskeleton, Structural protein Contig35002_RC FLJ12994 hypothetical protein Hypothetical protein 865 4833 FLJ12994 Contig35018_RC zr44a03.s1 866 4834 Soares_NhHMPu_S 1 Homo sapiens cDNA clone IMAGE: 666220 3′, mRNA sequence. Contig35043 Transcribed 867 4835 sequences Contig35052_RC pituitary tumor- Transmembrane, Nuclear protein 868 4836 transforming 1 interacting protein Contig35076_RC Sequence 226 from 869 4837 Patent WO0220754. Contig35094_RC FLJ21478 NOD9 protein Hypothetical protein 870 4838 Contig35163_RC Similar to 871 4839 hypothetical protein MG11009.4 (LOC285344), mRNA Contig35182_RC qb88b05.x1 872 4840 Soares_fetal_heart_NbHH19W Homo sapiens cDNA clone IMAGE: 1707153 3′, mRNA sequence. Contig35187_RC ARL4 ADP-ribosylation GTP-binding, Multigene family, 873 4841 factor-like 4 Nuclear protein Contig35251_RC CDNA: FLJ22719 874 4842 fis, clone HSI14307 Contig35425_RC hypothetical protein Hypothetical protein 875 4843 LOC285831 Contig35435_RC FLJ23447 hypothetical protein Hypothetical protein 876 4844 FLJ23447 Contig35576_RC Transcribed 877 4845 sequences Contig35608_RC df54a02.y1 Morton 878 4846 Fetal Cochlea Homo sapiens cDNA clone IMAGE: 2487051 5′, mRNA sequence. Contig35635_RC TAGAP T-cell activation Hypothetical protein 879 4847 GTPase activating protein Contig35661_RC DSCR1L2 Down syndrome Alternative splicing 880 4848 critical region gene 1-like 2 Contig35685_RC FLJ13117 spermatogenesis Hypothetical protein 881 4849 associated, serine- rich 2 Contig35700_RC CDNA clone 882 4850 IMAGE: 6702802, partial cds Contig35713_RC FIS 883 4851 Contig35799_RC centaurin, beta 2 GTPase activation, Repeat, ANK 884 4852 repeat, Zinc-finger Contig35874_RC Transcribed 885 4853 sequences Contig35896_RC signal transducer Hypothetical protein, Repeat, WD 886 4854 and activator of repeat transcription 3 interacting protein 1 Contig35940 KIAA1733 RPEL repeat Hypothetical protein 887 4855 containing 1 Contig35958_RC MGC13071 hypothetical protein Hypothetical protein, Metal-binding, 888 4856 MGC13071 Nuclear protein, Zinc, Zinc-finger Contig35976_RC family with sequence Signal 889 4857 similarity 3, member C Contig3597_RC LENG5 leukocyte receptor Receptor, Hypothetical protein 890 4858 cluster (LRC) member 5 Contig36020_RC MGC15634 hypothetical protein Hypothetical protein 891 4859 MGC15634 Contig36075_RC Transcribed 892 4860 sequences Contig36104_RC CCT6A Iaa10b09.x1 8 5 Chaperone, ATP-binding, Multigene 893 4861 week embryo family anterior tongue 8 5 EAT Homo sapiens cDNA 3′, mRNA sequence. Contig36106_RC NCL hypothetical protein Hypothetical protein 894 4862 LOC157697 Contig36125_RC Transcribed 895 4863 sequences Contig36129_RC MGC4707 hypothetical protein Hypothetical protein 896 4864 LOC283989 Contig3612_RC KIAA1802 chromosome 13 Hypothetical protein, Metal-binding, 897 4865 open reading frame 8 Zinc, Zinc-finger Contig36152_RC sterile alpha motif Hypothetical protein, ANK repeat, 898 4866 domain containing 6 Repeat Contig36169_RC DKFZp547E052 hypothetical protein Hypothetical protein 899 4867 DKFZp547E052 Contig36178_RC sialyltransferase 9 Transferase, Glycosyltransferase, 900 4868 (CMP- Glycoprotein, Transmembrane, NeuAc:lactosylceramide Signal-anchor, Golgi stack alpha-2,3- sialyltransferase; GM3 synthase) Contig36190_RC Transcribed 901 4869 sequences Contig36193_RC inositol 1,4,5- Receptor, Transmembrane, 902 4870 triphosphate Phosphorylation, Ionic channel, Ion receptor, type 1 transport, Calcium channel Contig36195_RC Full length insert 903 4871 cDNA clone ZD73D05 Contig3626_RC FLJ13855 hypothetical protein Hypothetical protein, Ligase, Ubl 904 4872 FLJ13855 conjugation pathway Contig36323_RC SFXN5 sideroflexin 5 Transport, Iron transport, Iron, 905 4873 Mitochondrion, Transmembrane Contig36359_RC Transcribed 906 4874 sequences Contig36369_RC we24d02.x1 907 4875 NCI_CGAP_Lu24 Homo sapiens cDNA clone IMAGE: 2342019 3′, mRNA sequence. Contig36409_RC Transcribed 908 4876 sequences Contig36512_RC Transcribed 909 4877 sequences Contig36525 ARX aristaless related Homeobox, DNA-binding, 910 4878 homeobox Developmental protein, Nuclear protein, Transcription regulation, Disease mutation, Triplet repeat expansion, Epilepsy Contig36617_RC chromosome 6 open 911 4879 reading frame 182 Contig36622_RC Transcribed 912 4880 sequences Contig36628 HANP1 913 4881 Contig36634_RC FLJ39514 sec1 family domain Hypothetical protein 914 4882 containing 2 Contig36720_RC Transcribed 915 4883 sequences Contig36761_RC FLJ23403 hypothetical protein Hypothetical protein 916 4884 FLJ23403 Contig36803_RC FLJ13952 sorting nexin 22 Hypothetical protein, Transport, 917 4885 Protein transport Contig36805_RC MGC15435 zinc finger, BED Zinc-finger 918 4886 domain containing 3 Contig36810 CDNA FLJ37425 fis, 919 4887 clone BRAWH2001530 Contig36876_RC Homo sapiens cDNA 920 4888 FLJ32044 fis, clone NTONG2000985. Contig36879_RC Clone 921 4889 IMAGE: 4753714, mRNA Contig36888_RC suppression of Hypothetical protein 922 4890 tumorigenicity 7 like Contig36939_RC Transcribed 923 4891 sequences Contig3695_RC MGC17330 HGFL gene Hypothetical protein, Glycoprotein, 924 4892 Kringle Contig36973_RC AGMAT Homo sapiens Putrescine biosynthesis, Spermidine 925 4893 cDNA: FLJ23384 fis, biosynthesis, Hydrolase, clone HEP16468. Manganese, Mitochondrion, Transit peptide Contig36976_RC DIBD1 disrupted in bipolar Hypothetical protein 926 4894 affective disorder 1 Contig36997_RC bioref zinc finger protein Transcription regulation, DNA- 927 4895 481 binding, Zinc-finger, Metal-binding, Nuclear protein, Repeat Contig37016_RC ING5 inhibitor of growth Hypothetical protein 928 4896 family, member 5 Contig37025_RC CDNA FLJ41484 fis, 929 4897 clone BRTHA2003030 Contig37029_RC FLJ23153 likely ortholog of Hypothetical protein 930 4898 mouse tumor necrosis-alpha- induced adipose- related protein Contig37037_RC chromosome 13 931 4899 open reading frame 25 Contig37082_RC MGC2408 hypothetical protein Hypothetical protein 932 4900 MGC2408 Contig37140_RC membrane protein, Hypothetical protein, SH3 domain 933 4901 palmitoylated 7 (MAGUK p55 subfamily member 7) Contig37142_RC Homo sapiens cDNA 934 4902 FLJ12163 fis, clone MAMMA1000594. Contig37219 MDN1 MDN1, midasin Chaperone, ATP-binding, Repeat, 935 4903 homolog (yeast) Nuclear protein Contig37262 Clone Hypothetical protein 936 4904 IMAGE: 5263527, mRNA Contig37300_RC KIAA1904 KIAA1904 protein Hypothetical protein 937 4905 Contig37306_RC MUC16 mucin 16 Hypothetical protein 938 4906 Contig3734_RC RPS8 Clone Ribosomal protein 939 4907 IMAGE: 4249217, mRNA Contig37361_RC Transcribed 940 4908 sequences Contig37364_RC Transcribed 941 4909 sequences Contig37368_RC nemo like kinase ATP-binding, Kinase, 942 4910 Serine/threonine-protein kinase, Transferase Contig37569_RC CDNA FLJ26339 fis, 943 4911 clone HRT02975 Contig37660_RC ADAM6 a disintegrin and 944 4912 metalloproteinase domain 6 Contig37736_RC RAD1 Transcribed Hypothetical protein, Ribosome 945 4913 sequence with biogenesis, Nuclear protein, Cell moderate similarity cycle, Exonuclease to protein ref: NP_060312.1 (H. sapiens) hypothetical protein FLJ20489 [Homo sapiens] Contig37763_RC Transcribed 946 4914 sequence with moderate similarity to protein ref: NP_002945.1 (H. sapiens) ubiquitin and ribosomal protein S27a precursor; ubiquitin carboxyl extension protein 80; 40S ribosomal protein S27a; ubiquitin; ubiquitin- CEP80 [Homo sapiens] Contig37764_RC qa65f01.x1 947 4915 Soares_fetal_heart_NbHH19W Homo sapiens cDNA clone IMAGE: 1691641 3′, mRNA sequence. Contig37895_RC yh88d01.s1 Soares 948 4916 placenta Nb2HP Homo sapiens cDNA clone IMAGE: 136801 3′, mRNA sequence. Contig37950_RC qz91d12.x1 949 4917 Soares_pregnant_uterus_NbHPU Homo sapiens cDNA clone IMAGE: 2041943 3′, mRNA sequence. Contig37958 KAI1 hypothetical protein Glycoprotein, Transmembrane, 950 4918 LOC284023 Antigen Contig37991_RC LOC133308 hypothetical protein Hypothetical protein 951 4919 BC009732 Contig38043_RC hypothetical protein 952 4920 LOC199675 Contig38093_RC Transcribed 953 4921 sequences Contig380_RC KIAA1724 selenoprotein I, 1 Hypothetical protein, Transferase, 954 4922 Transmembrane, Selenium, Selenocysteine Contig38117_RC Transcribed 955 4923 sequences Contig38155_RC Transcribed 956 4924 sequences Contig38169_RC FLJ13984 hypothetical protein Hypothetical protein 957 4925 FLJ13984 Contig3820_RC LOC56898 dehydrogenase/reductase Oxidoreductase, Hypothetical protein 958 4926 (SDR family) member 6 Contig38285_RC FLJ10462 male sterility domain Hypothetical protein 959 4927 containing 1 Contig38288_RC DKFZp762A2013 quiescin Q6-like 1 Hypothetical protein, Signal 960 4928 Contig382_RC NLI-IF CTD (carboxy- Hypothetical protein, Nuclear protein 961 4929 terminal domain, RNA polymerase II, polypeptide A) small phosphatase 1 Contig38320_RC Transcribed 962 4930 sequences Contig38321_RC Transcribed 963 4931 sequences Contig3834_RC MRNA; cDNA 964 4932 DKFZp686K14148 (from clone DKFZp686K14148) Contig38398_RC Transcribed 965 4933 sequences Contig38493_RC CDNA FLJ42010 fis, 966 4934 clone SPLEN2032036 Contig38581_RC anaphase promoting Ubl conjugation pathway, Cell cycle, 967 4935 complex subunit 1 Cell division, Mitosis, Repeat Contig38603_RC Transcribed 968 4936 sequences Contig38604_RC CDNA FLJ25042 fis, Hypothetical protein 969 4937 clone CBL03351 Contig38654_RC solute carrier family 970 4938 28 (sodium-coupled nucleoside transporter), member 3 Contig38669_RC HS2ST1 heparan sulfate 2-O- Hypothetical protein, Transferase 971 4939 sulfotransferase 1 Contig38714_RC Transcribed 972 4940 sequences Contig38721_RC MGC35163 sterile alpha motif Hypothetical protein 973 4941 domain containing 3 Contig38724_RC Clone 974 4942 IMAGE: 5275753, mRNA Contig38726_RC SWI/SNF related, Hypothetical protein 975 4943 matrix associated, actin dependent regulator of chromatin, subfamily e, member 1 Contig38731_RC frizzled homolog 2 Multigene family, G-protein coupled 976 4944 (Drosophila) receptor, Transmembrane, Developmental protein, Wnt signaling pathway, Glycoprotein, Signal Contig38778 TRIM7 tripartite motif- Zinc-finger, Zinc, Coiled coil, Metal- 977 4945 containing 7 binding, Polymorphism, Alternative splicing Contig38803_RC Rho GTPase GTPase activation, SH3-binding, 3D- 978 4946 activating protein 1 structure Contig38877 zv94e09.s1 979 4947 Soares_NhHMPu_S1 Homo sapiens cDNA clone IMAGE: 767464 3′, mRNA sequence. Contig38944_RC Transcribed 980 4948 sequences Contig39008_RC MYCL1 v-myc Nuclear protein, DNA-binding, Proto- 981 4949 myelocytomatosis oncogene viral oncogene homolog 1, lung carcinoma derived (avian) Contig39043_RC zl77f02.s1 982 4950 Stratagene colon (#937204) Homo sapiens cDNA clone IMAGE: 510651 3′, mRNA sequence. Contig39048_RC TAFA2 protein Hypothetical protein 983 4951 Contig39116_RC a1/3GTP alpha-1,3- Glycosyltransferase, Transferase 984 4952 galactosyltransferase pseudogene Contig3920_RC SP1 Sp1 transcription Hypothetical protein, Transcription 985 4953 factor regulation, Activator, Zinc-finger, Metal-binding, DNA-binding, Nuclear protein, Repeat, Glycoprotein, 3D- structure Contig39236 FLJ00026 Homo sapiens, Hypothetical protein, Guanine- 986 4954 Similar to RIKEN nucleotide releasing factor cDNA 5830472H07 gene, clone MGC: 39702 IMAGE: 5271738, mRNA, complete cds. Contig39249 THBS3 thrombospondin 3 Glycoprotein, Cell adhesion, 987 4955 Calcium-binding, Repeat, EGF-like domain, Signal Contig39287_RC Transcribed 988 4956 sequence with moderate similarity to protein pir: E54024 (H. sapiens) E54024 protein kinase Contig39297_RC LOC148898 hypothetical protein Hypothetical protein 989 4957 BC007899 Contig39364_RC UPF3B UPF3 regulator of 990 4958 nonsense transcripts homolog B (yeast) Contig39403_RC hypothetical protein Hypothetical protein 991 4959 FLJ34790 Contig3940_RC C9orf19 chromosome 9 open Hypothetical protein 992 4960 reading frame 19 Contig39448_RC N-acetylneuraminate 993 4961 pyruvate lyase (dihydrodipicolinate synthase) Contig39496_RC FLJ22501 Hermansky-Pudlak Hypothetical protein 994 4962 syndrome 6 Contig39545_RC MTIF3 general transcription Transcription regulation, Zinc-finger, 995 4963 factor IIIA Metal-binding, DNA-binding, RNA- binding, Repeat, Nuclear protein, Polymorphism Contig39603_RC CNOT3 CCR4-NOT Hypothetical protein 996 4964 transcription complex, subunit 3 Contig39626_RC STK35 serine/threonine Hypothetical protein, Transferase, 997 4965 kinase 35 Serine/threonine-protein kinase, ATP-binding, Phosphorylation Contig39702_RC similar to Putative Hypothetical protein 998 4966 protein C21orf56 Contig39739_RC CDK9 Full length insert Transferase, Serine/threonine- 999 4967 cDNA clone protein kinase, ATP-binding, Nuclear ZA91F08 protein, Polymorphism Contig39797_RC TRIPIN tripin Hypothetical protein 1000 4968 Contig39810_RC hypothetical protein Hypothetical protein 1001 4969 MGC43690 Contig39878_RC BOP SET and MYND Transcription regulation, Repressor, 1002 4970 domain containing 1 DNA-binding, Nuclear protein, Zinc- finger, Metal-binding Contig39933_RC LOC90693 Sequence 2 from Hypothetical protein 1003 4971 Patent WO0220754. Contig39989_RC MGC14289 similar to RIKEN 1004 4972 cDNA 1200014N16 gene Contig40015_RC Transcribed 1005 4973 sequence with moderate similarity to protein pdb: 1LBG (E. coli) B Chain B, Lactose Operon Repressor Bound To 21-Base Pair Symmetric Operator Dna, Alpha Carbons Only Contig40026_RC CDNA FLJ12935 fis, 1006 4974 clone NT2RP2004982 Contig40053_RC HNRPD heterogeneous Nuclear protein, RNA-binding, DNA- 1007 4975 nuclear binding, Ribonucleoprotein, Repeat, ribonucleoprotein D Transcription regulation, Telomere, (AU-rich element Alternative splicing, 3D-structure RNA binding protein 1, 37 kDa) Contig40055_RC Transcribed 1008 4976 sequences Contig40069_RC Transcribed 1009 4977 sequences Contig40093_RC fatty acid binding Transport, Lipid-binding, Acetylation, 1010 4978 protein 3, muscle Phosphorylation, 3D-structure and heart (mammary-derived growth inhibitor) Contig40094_RC DKFZp434I099 hypothetical protein Hypothetical protein 1011 4979 DKFZp434I099 Contig40128_RC hypoxia-inducible Transcription regulation, Activator, 1012 4980 factor 1, alpha Nuclear protein, DNA-binding, subunit (basic helix- Alternative splicing, Repeat, loop-helix Acetylation, Hydroxylation, transcription factor) Phosphorylation, S-nitrosylation, Polymorphism, 3D-structure Contig40184 SLC2A1 solute carrier family Transmembrane, Sugar transport, 1013 4981 2 (facilitated glucose Transport, Glycoprotein, Multigene transporter), family, Disease mutation, 3D- member 1 structure Contig40212_RC CD5 CD5 antigen (p56- Signal, Transmembrane, 1014 4982 62) Glycoprotein, T-cell, Repeat Contig40237_RC FLJ12525 hypothetical protein Hypothetical protein 1015 4983 FLJ12525 Contig40252_RC CDNA clone Hypothetical protein 1016 4984 IMAGE: 3462401, partial cds Contig40340_RC hypothetical protein Hypothetical protein 1017 4985 FLJ11000 Contig40389_RC Similar to RIKEN 1018 4986 cDNA 3830422K02 (LOC387755), mRNA Contig404 Mesenchymal stem 1019 4987 cell protein DSC96 mRNA, partial cds Contig40405_RC MGC10818 chromosome 6 open Hypothetical protein 1020 4988 reading frame 148 Contig40410 tc14e12.x1 Hypothetical protein 1021 4989 Soares_NhHMPu_S1 Homo sapiens cDNA clone IMAGE: 2063854 3′, mRNA sequence. Contig40450_RC THAP domain Hypothetical protein 1022 4990 containing 9 Contig40552_RC FLJ25348 hypothetical protein Hypothetical protein 1023 4991 FLJ25348 Contig40651_RC Transcribed 1024 4992 sequences Contig40676_RC Sequence 60 from 1025 4993 Patent WO0220754. Contig40830_RC TSGA14 testis specific, 14 Hypothetical protein 1026 4994 Contig40832_RC Transcribed 1027 4995 sequences Contig40897_RC DKFZP434J037 likely ortholog of rat Hypothetical protein, ATP-binding, 1028 4996 SNF1/AMP-activated Kinase, Serine/threonine-protein protein kinase kinase, Transferase Contig40960_RC FLJ36991 zinc finger protein Hypothetical protein, Metal-binding, 1029 4997 565 Nuclear protein, Zinc, Zinc-finger Contig40965_RC MGC4504 hypothetical protein Hypothetical protein 1030 4998 MGC4504 Contig40967_RC LOC389388 1031 4999 (LOC389388), mRNA Contig41005_RC Transcribed 1032 5000 sequence with strong similarity to protein pdb: 1BGM (E. coli) O Chain O, Beta-Galactosidase Contig41035 golgi phosphoprotein 4 1033 5001 Contig41041_RC CDNA FLJ32274 fis, 1034 5002 clone PROST2000036 Contig41080_RC Transcribed 1035 5003 sequences Contig41086_RC forkhead box P1 Hypothetical protein, Transcription 1036 5004 regulation, DNA-binding, Zinc-finger, Metal-binding, Nuclear protein, Alternative splicing Contig41094_RC EDG8 endothelial Hypothetical protein, Receptor 1037 5005 differentiation, sphingolipid G- protein-coupled receptor, 8 Contig41121_RC FCRH3 Fc receptor-like Immunoglobulin domain, Receptor 1038 5006 protein 3 Contig41209_RC FLJ21432 adiponectin receptor 2 Fatty acid metabolism, Lipid 1039 5007 metabolism, Receptor, Transmembrane Contig41226_RC MRNA; cDNA Hypothetical protein 1040 5008 DKFZp434O232 (from clone DKFZp434O232) Contig412_RC FLJ22233 Homo sapiens cDNA Hypothetical protein 1041 5009 FLJ36755 fis, clone UTERU2018180, weakly similar to Na+/Ca2+, K+- exchanging protein homolog C13D9.8. Contig41301 LOC152217 hypothetical protein Hypothetical protein 1042 5010 BC007882 Contig41421_RC FLJ36156 piwi-like 2 Hypothetical protein 1043 5011 (Drosophila) Contig41448_RC dynamin 1-like 1044 5012 Contig41537 MGC20496 methylmalonic Transferase, Mitochondrion, Transit 1045 5013 aciduria (cobalamin peptide, Polymorphism, Disease deficiency) type B mutation Contig41560_RC CPT1A carnitine Transferase, Acyltransferase, 1046 5014 palmitoyltransferase Mitochondrion, Outer membrane, 1A (liver) Fatty acid metabolism, Transport, Transmembrane, Multigene family Contig41612_RC hypothetical protein Hypothetical protein 1047 5015 LOC132241 Contig41618_RC Clone Hypothetical protein 1048 5016 IMAGE: 5315196, mRNA Contig41638_RC SLC26A8 solute carrier family 1049 5017 26, member 8 Contig41656_RC Similar to Eph 1050 5018 receptor A7, clone IMAGE: 5273054, mRNA Contig41701_RC Transcribed 1051 5019 sequences Contig41748_RC ELMO3 engulfment and cell Apoptosis, Phagocytosis, 1052 5020 motility 3 (ced-12 Cytoskeleton, Membrane, SH3- homolog, C. elegans) binding Contig41774_RC Transcribed 1053 5021 sequences Contig41781_RC ARHGEF7 Rho guanine Guanine-nucleotide releasing factor, 1054 5022 nucleotide exchange SH3 domain, Alternative splicing, factor (GEF) 7 3D-structure, Hypothetical protein Contig41828_RC Clone 1055 5023 IMAGE: 5310874, mRNA Contig41864_RC ZFP106 zinc finger protein Hypothetical protein, Metal-binding, 1056 5024 106 homolog Repeat, WD repeat, Zinc, Zinc-finger (mouse) Contig41869_RC SFRS3 splicing factor, Nuclear protein, RNA-binding, 1057 5025 arginine/serine-rich 3 mRNA splicing, Alternative splicing, Phosphorylation, Repeat Contig41903_RC FLJ21657 hypothetical protein Hypothetical protein 1058 5026 FLJ21657 Contig41923_RC OATL1 ornithine Transferase, Aminotransferase 1059 5027 aminotransferase- like 1 Contig41936_RC MSL3L1 male-specific lethal Chromatin regulator, Nuclear 1060 5028 3-like 1 (Drosophila) protein, Transcription regulation, Alternative splicing Contig41983_RC ym35b12.s1 Soares 1061 5029 infant brain 1NIB Homo sapiens cDNA clone IMAGE: 50144 3′, mRNA sequence. Contig42005_RC splicing factor, Nuclear protein, RNA-binding, 1062 5030 arginine/serine-rich mRNA splicing, Repeat 11 Contig42006_RC RasGEF domain Hypothetical protein 1063 5031 family, member 1B Contig42012_RC zinc finger, DHHC Transmembrane, Zinc-finger 1064 5032 domain containing 21 Contig42014_RC RNTRE USP6 N-terminal like Hypothetical protein 1065 5033 Contig42076_RC FLJ39091 zinc binding alcohol Hypothetical protein 1066 5034 dehydrogenase, domain containing 1 Contig42105_RC MRNA; cDNA 1067 5035 DKFZp686P24244 (from clone DKFZp686P24244) Contig42146_RC chromosome 19 Hypothetical protein 1068 5036 open reading frame 12 Contig42154_RC FLJ11795 hypothetical protein Hypothetical protein 1069 5037 FLJ11795 Contig42174 FLJ33215 hypothetical protein Hypothetical protein 1070 5038 FLJ33215 Contig42177_RC zinc finger, DHHC Hypothetical protein, 1071 5039 domain containing Transmembrane, Zinc-finger 19 Contig42185_RC TLR8 toll-like receptor 8 Hypothetical protein, Receptor, 1072 5040 Immune response, Inflammatory response, Signal, Transmembrane, Repeat, Leucine-rich repeat, Glycoprotein Contig421_RC KIAA1821 rab11-family Hypothetical protein 1073 5041 interacting protein 4 Contig42256_RC Transcribed 1074 5042 sequences Contig42263_RC PSMB5 ATP synthase, H+ Hydrogen ion transport, CF(0), 1075 5043 transporting, Mitochondrion, Transit peptide, mitochondrial F0 Hypothetical protein complex, subunit s (factor B) Contig42270_RC similar to metallo- Hypothetical protein 1076 5044 beta-lactamase superfamily protein Contig42330_RC Transcribed 1077 5045 sequences Contig42342_RC CDNA FLJ39417 fis, Hypothetical protein 1078 5046 clone PLACE6016942 Contig42418_RC Transcribed 1079 5047 sequence with weak similarity to protein ref: NP_060265.1 (H. sapiens) hypothetical protein FLJ20378 [Homo sapiens] Contig42437_RC C1orf28 casein kinase 1, Transferase, Serine/threonine- 1080 5048 epsilon protein kinase, ATP-binding, Phosphorylation, Multigene family Contig42459_RC FLJ22021 hypothetical protein Repeat, WD repeat 1081 5049 FLJ22021 Contig42566_RC FLJ14761 hypothetical protein Hypothetical protein 1082 5050 FLJ14761 Contig42591_RC shadow of prion 1083 5051 protein Contig42593_RC Transcribed 1084 5052 sequences Contig42597_RC wd88a09.x1 1085 5053 NCI_CGAP_Lu24 Homo sapiens cDNA clone IMAGE: 2338648 3′, mRNA sequence. Contig42615_RC AMID apoptosis-inducing Hypothetical protein 1086 5054 factor (AIF)- homologous mitochondrion- associated inducer of death Contig42617_RC SNRPG Human S6 H-8 Ubiquitin conjugation, Hydrolase, 1087 5055 mRNA expressed in Thiol protease, Multigene family, chromosome 6- Alternative splicing suppressed melanoma cells. Contig42666_RC chromosome 10 Hypothetical protein 1088 5056 open reading frame 47 Contig42759_RC BCL11B B-cell B-cell, Metal-binding, Zinc, Zinc- 1089 5057 CLL/lymphoma 11B finger (zinc finger protein) Contig42787_RC hypothetical protein Hypothetical protein 1090 5058 MGC5509 Contig42824_RC FLJ10785 ubiquitin specific Ubl conjugation pathway, Hydrolase, 1091 5059 protease 40 Thiol protease, Alternative splicing, Polymorphism, multigene family Contig42854 CDNA FLJ33578 fis, 1092 5060 clone BRAMY2011639 Contig42903_RC Transcribed 1093 5061 sequence with strong similarity to protein ref: NP_002745.1 (H. sapiens) mitogen-activated protein kinase 13; mitogen-activated protein kinase p38 delta; stress- activated protein kianse 4 [Homo sapiens] Contig42959_RC solute carrier family Hypothetical protein 1094 5062 5 (sodium/glucose cotransporter), member 10 Contig42962_RC Transcribed 1095 5063 sequence with weak similarity to protein pir: S41161 (H. sapiens) S41161 keratin 9, cytoskeletal - human Contig43022_RC similar to RIKEN 1096 5064 cDNA 2610524G09 Contig43026_RC hypothetical protein Hypothetical protein 1097 5065 DKFZp762C1112 Contig43096_RC Clone 1098 5066 IMAGE: 5743799, mRNA Contig43169_RC DEAD (Asp-Glu-Ala- ATP-binding, Helicase, Hydrolase, 1099 5067 Asp) box polypeptide Hypothetical protein 51 Contig43184_RC yg20d12.s1 Soares 1100 5068 infant brain 1NIB Homo sapiens cDNA clone IMAGE: 32918 3′, mRNA sequence. Contig43189_RC Transcribed 1101 5069 sequences Contig43241_RC ADCY7 adenylate cyclase 7 Lyase, cAMP biosynthesis, 1102 5070 Transmembrane, Glycoprotein, Repeat, Metal-binding, Magnesium Contig43253_RC KIAA1858 zinc finger protein Transcription regulation, DNA- 1103 5071 469 binding, Zinc-finger, Metal-binding, Nuclear protein, Repeat Contig43262_RC Transcribed 1104 5072 sequences Contig43277_RC Similar to KIAA1726 1105 5073 protein (LOC340554), mRNA Contig43289_RC hypothetical protein 1106 5074 LOC170371 Contig43385_RC DKFZp762O076 hypothetical protein Hypothetical protein 1107 5075 DKFZp762O076 Contig43436_RC FLJ32028 hypothetical protein Hypothetical protein 1108 5076 FLJ32028 Contig43486_RC DRB1 developmentally Hypothetical protein 1109 5077 regulated RNA- binding protein 1 Contig43506_RC GLI pathogenesis- 1110 5078 related 1 (glioma) Contig43513_RC TIGD7 Homo sapiens cDNA 1111 5079 FLJ13533 fis, clone PLACE1006371. Contig43534 ankyrin repeat Hypothetical protein, ANK repeat, 1112 5080 domain 10 Repeat Contig43540_RC GRIM19 FLJ44968 protein Oxidoreductase, Ubiquinone, NAD, 1113 5081 Apoptosis, Mitochondrion, Transmembrane, Acetylation, Hypothetical protein Contig43542_RC KIAA1718 protein Hypothetical protein 1114 5082 Contig43549_RC SNX5 Homo sapiens, clone Hypothetical protein, Transport, 1115 5083 MGC: 3411 Protein transport IMAGE: 3629947, mRNA, complete cds. Contig43586_RC hypothetical protein 1116 5084 LOC134218 Contig43645_RC hypothetical protein Hypothetical protein 1117 5085 LOC129607 Contig43655_RC NAG14 leucine rich repeat Immunoglobulin domain, 1118 5086 containing 4 Hypothetical protein, Signal Contig43658_RC likely ortholog of 1119 5087 mouse cancer related gene - liver 2 Contig4365_RC TGOLN2 trans-golgi network Hypothetical protein, Signal, 1120 5088 protein 2 Transmembrane, Glycoprotein, Repeat, Golgi stack, Alternative splicing Contig43673_RC FLJ20481 calpain small subunit 2 Hypothetical protein 1121 5089 Contig43679_RC MEF-2 myelin expression Hypothetical protein 1122 5090 factor 2 Contig43694_RC TSPAN-2 tetraspan 2 Glycoprotein, Transmembrane 1123 5091 Contig43703_RC CDH13 CDNA FLJ25967 fis, Cell adhesion, Glycoprotein, 1124 5092 clone CBR01929 Calcium-binding, Repeat, GPI- anchor, Signal Contig43724_RC FLJ13213 hypothetical protein Hypothetical protein 1125 5093 FLJ13213 Contig43746_RC CDNA FLJ41107 fis, 1126 5094 clone BLADE2007923 Contig43749_RC MGC14258 Rho GTPase Hypothetical protein 1127 5095 activating protein 19 Contig43750_RC cleavage and 1128 5096 polyadenylation specific factor 6, 68 kDa Contig43817_RC RINZF zinc finger and BTB Hypothetical protein, Metal-binding, 1129 5097 domain containing Zinc, Zinc-finger 10 Contig438_RC hypothetical protein EGF-like domain, Hypothetical 1130 5098 MGC61716 protein Contig4399_RC MYH9 myosin, heavy Myosin, ATP-binding, Calmodulin- 1131 5099 polypeptide 9, non- binding, Actin-binding, Coiled coil, muscle Multigene family, Disease mutation, Deafness, Hypothetical protein Contig440 MGC3165 Homo sapiens, H2A Acetylation, Chromosomal 1132 5100 histone family, protein, DNA-binding, Multigene member L, clone family, Nuclear protein, Nucleosome MGC: 3165 core IMAGE: 3355200, mRNA, complete cds. Contig44059_RC hypothetical protein Hypothetical protein 1133 5101 DKFZp564B1162 Contig44078 TA-WDRP T-cell activation WD Hypothetical protein, Repeat, WD 1134 5102 repeat protein repeat Contig44105 OSBPL11 oxysterol binding Hypothetical protein, Lipid transport, 1135 5103 protein-like 11 Transport Contig44124_RC CDNA FLJ30906 fis, Hypothetical protein 1136 5104 clone FEBRA2006055 Contig44133_RC FLJ11362 hypothetical protein Hypothetical protein, ANK repeat, 1137 5105 FLJ11362 Repeat Contig44192_RC Cas-Br-M (murine) Hypothetical protein, Ligase, Ubl 1138 5106 ecotropic retroviral conjugation pathway, Proto- transforming oncogene, Zinc-finger, SH2 domain, sequence Phosphorylation, Calcium-binding, 3D-structure Contig44226_RC TIGD2 tigger transposable 1139 5107 element derived 2 Contig44265_RC ATPase, Hydrolase, Transmembrane, 1140 5108 aminophospholipid Phosphorylation, Magnesium, ATP- transporter (APLT), binding, Alternative splicing, Class I, type 8A, Multigene family member 1 Contig44278_RC DKFZp434K114 WD repeat domain Repeat, WD repeat, Hypothetical 1141 5109 21 protein, Plasmid Contig44343 CDNA FLJ26676 fis, 1142 5110 clone MPG03726 Contig44358_RC DKFZp434N035 Hypothetical Hypothetical protein 1143 5111 LOC284874 (LOC284874), mRNA Contig44409 similar to LL5 beta Hypothetical protein 1144 5112 Contig44414_RC SLC30A1 solute carrier family Zinc transport, Transport, 1145 5113 30 (zinc transporter), Transmembrane, Multigene family member 1 Contig44492_RC Transcribed 1146 5114 sequences Contig44518_RC FAM11A family with sequence Antigen, Multigene family, Tumor 1147 5115 similarity 11, antigen, Hypothetical protein member A Contig44521_RC LSM8 homolog, U6 Nuclear protein, Ribonucleoprotein, 1148 5116 small nuclear RNA mRNA splicing, mRNA processing, associated (S. cerevisiae) RNA-binding, Acetylation Contig44548_RC hypothetical protein 1149 5117 LOC283508 Contig44593_RC retinoblastoma Hypothetical protein, Metal-binding, 1150 5118 binding protein 6 Zinc, Zinc-finger Contig44595_RC hypothetical protein Hypothetical protein 1151 5119 MGC45840 Contig44596_RC PPIL3 peptidylprolyl Isomerase, Rotamase, Hypothetical 1152 5120 isomerase protein (cyclophilin)-like 3 Contig44708_RC BCAT1 Homo sapiens Hypothetical protein, Transferase, 1153 5121 cDNA: FLJ21270 fis, Aminotransferase, Branched-chain clone COL01749. amino acid biosynthesis, Pyridoxal phosphate Contig44713 transducin-like Transcription regulation, Repressor, 1154 5122 enhancer of split 4 Nuclear protein, Repeat, WD repeat, (E(sp1) homolog, Phosphorylation, Wnt signaling Drosophila) pathway Contig44720_RC FKSG32 hypothetical protein Hypothetical protein 1155 5123 FKSG32 Contig44723_RC Human cAMP- 1156 5124 binding guanine nucleotide exchange factor IV (cAMP- GEFIV) mRNA, clone W15, partial sequence Contig44757_RC VIM Transcribed Hypothetical protein, Coiled coil, 1157 5125 sequence with Intermediate filament, strong similarity to Phosphorylation, 3D-structure protein pir: A25074 (H. sapiens) A25074 vimentin - human Contig44817_RC C20orf147 chromosome 20 Hydrolase 1158 5126 open reading frame 147 Contig44874_RC LOC57805 p30 DBC protein Hypothetical protein 1159 5127 Contig44877_RC KIAA1877 beta-galactoside Hypothetical protein, Transferase, 1160 5128 alpha-2,6- Glycosyltransferase sialyltransferase II Contig44964_RC hypothetical gene 1161 5129 supported by BC017510; BC046919 Contig45004_RC hypothetical protein 1162 5130 LOC283129 Contig45080_RC CUL5 cullin 5 Ubl conjugation pathway, Ubl 1163 5131 conjugation, Receptor Contig45085_RC ATP6V0A2 Homo sapiens cDNA Hydrogen ion transport, 1164 5132 FLJ32238 fis, clone Transmembrane, Glycoprotein, PLACE6004993. Hypothetical protein Contig45135 CDNA: FLJ22382 1165 5133 fis, clone HRC07514 Contig45201_RC C1QTNF2 C1q and tumor Collagen, Signal 1166 5134 necrosis factor related protein 2 Contig45290_RC Similar to RIKEN 1167 5135 cDNA 3010021M21 (LOC388185), mRNA Contig45304_RC DEPC-1 prostate cancer 1168 5136 antigen-1 Contig45305_RC MGC3130 hypothetical protein Hypothetical protein 1169 5137 MGC3130 Contig45328_RC Similar to Ab2-183 1170 5138 (LOC158830), mRNA Contig45338_RC CSNK2A1 casein kinase 2, Transferase, Serine/threonine- 1171 5139 alpha 1 polypeptide protein kinase, ATP-binding, Wnt signaling pathway, 3D-structure Contig45377_RC C10orf2 progressive external Hypothetical protein, Helicase 1172 5140 ophthalmoplegia 1 Contig45381_RC hypothetical protein 1173 5141 LOC283663 Contig45396_RC FLJ13197 hypothetical protein Hypothetical protein 1174 5142 FLJ13197 Contig45397_RC FLJ34299 zinc finger protein 92 Hypothetical protein, Metal-binding, 1175 5143 (HTF12) Nuclear protein, Zinc, Zinc-finger, Transcription regulation, DNA- binding, Repeat Contig45437 similar to RNA Hypothetical protein 1176 5144 polymerase B transcription factor 3 Contig45440_RC Similar to RIKEN 1177 5145 cDNA 9330196J05 (LOC340075), mRNA Contig45455_RC soluble liver 1178 5146 antigen/liver pancreas antigen Contig45457_RC CYP4F12 cytochrome P450, Oxidoreductase, Monooxygenase, 1179 5147 family 4, subfamily Electron transport, Membrane, F, polypeptide 12 Heme, Microsome, Endoplasmic reticulum, Polymorphism Contig45540_RC G protein-coupled Receptor 1180 5148 receptor 114 Contig45544_RC protein kinase, Hypothetical protein, Kinase 1181 5149 interferon-inducible double stranded RNA dependent activator Contig45569_RC CDC14B CDC14 cell division Hydrolase 1182 5150 cycle 14 homolog B (S. cerevisiae) Contig45624_RC HAKAI Cas-Br-M (murine) Hypothetical protein, Metal-binding, 1183 5151 ecotropic retroviral Zinc, Zinc-finger transforming sequence-like 1 Contig45634_RC Similar to FLJ46354 Hypothetical protein 1184 5152 protein (LOC389694), mRNA Contig45642_RC mitogen-activated ATP-binding, Kinase, Transferase, 1185 5153 protein kinase Serine/threonine-protein kinase, kinase kinase 2 Hypothetical protein Contig45790_RC KIAA0187 ESTs, Moderately 1186 5154 similar to KIAA0187 gene product [Homo sapiens] [H. sapiens] Contig45800_RC MTX1 metaxin 1 Mitochondrion, Outer membrane, 1187 5155 Transmembrane, Transport, Protein transport Contig45816_RC MGC4832 chromosome 13 Hypothetical protein 1188 5156 open reading frame 3 Contig45821_RC ADCY4 adenylate cyclase 4 Hypothetical protein, Lyase, cAMP 1189 5157 biosynthesis, Transmembrane, Glycoprotein, Repeat, Metal-binding, Magnesium Contig45847_RC DKFZP761I2123 hypothetical protein Hypothetical protein 1190 5158 DKFZp761I2123 Contig45879_RC KIAA1145 KIAA1145 protein Hypothetical protein, 1191 5159 Transmembrane Contig45891_RC CDNA FLJ37509 fis, 1192 5160 clone BRCAN1000065 Contig45944_RC ZNF335 zinc finger protein Transcription regulation, Zinc-finger, 1193 5161 335 Metal-binding, Nuclear protein, DNA- binding, Repeat Contig45945_RC Transcribed 1194 5162 sequences Contig4595 hypothetical Hypothetical protein 1195 5163 LOC387763 Contig45975_RC Transcribed 1196 5164 sequences Contig45984 USP7 ubiquitin specific Ubl conjugation pathway, Hydrolase, 1197 5165 protease 7 (herpes Thiol protease, Multigene family, virus-associated) Nuclear protein, 3D-structure Contig46052_RC ectonucleoside Hydrolase, Transmembrane, 1198 5166 triphosphate Antigen, Glycoprotein, Calcium, diphosphohydrolase 1 Magnesium, Alternative splicing, Lipoprotein, Palmitate Contig46178_RC Homo sapiens, clone 1199 5167 IMAGE: 5276307, mRNA. Contig461_RC KIAA1836 KIAA1836 protein Hypothetical protein 1200 5168 Contig46202 MAD MAX dimerization Nuclear protein, DNA-binding, 1201 5169 protein 1 Transcription regulation, Repressor, 3D-structure Contig46218_RC Similar to 1202 5170 diaphanous homolog 3 (Drosophila), clone IMAGE: 5277415, mRNA Contig46244_RC Clone 1203 5171 IMAGE: 111705 mRNA sequence Contig46262_RC Similar to 1204 5172 2010300C02Rik protein (LOC343990), mRNA Contig46265_RC LOH11CR1J gene, 1205 5173 loss of heterozygosity, 11, chromosomal region 1 gene J product Contig46294_RC Transcribed 1206 5174 sequence with weak similarity to protein ref: NP_060312.1 (H. sapiens) hypothetical protein FLJ20489 [Homo sapiens] Contig46306_RC CDNA FLJ36097 fis, 1207 5175 clone TESTI2020956 Contig46343_RC SPP1 suppressor of SH2 domain, Growth regulation, 1208 5176 cytokine signaling 7 Signal transduction inhibitor Contig46375_RC CDNA FLJ26349 fis, 1209 5177 clone HRT04618 Contig46376_RC zinc finger and BTB Hypothetical protein, Metal-binding, 1210 5178 domain containing Zinc, Zinc-finger 10 Contig46399_RC Transcribed 1211 5179 sequences Contig46416_RC MGC33212 hypothetical protein 1212 5180 MGC33212 Contig46421_RC Transcribed 1213 5181 sequence with moderate similarity to protein ref: NP_005496.1 (H. sapiens) CD36 antigen Contig46437_RC synaptotagmin Transport, Protein transport 1214 5182 binding, cytoplasmic RNA interacting protein Contig46443_RC solute carrier family Hypothetical protein 1215 5183 26, member 11 Contig46464_RC Transcribed 1216 5184 sequences Contig46482_RC MRNA; cDNA 1217 5185 DKFZp434C1435 (from clone DKFZp434C1435) Contig46506_RC MRNA; cDNA 1218 5186 DKFZp686C18110 (from clone DKFZp686C18110) Contig46536_RC LGI3 leucine-rich repeat Repeat, Leucine-rich repeat, Signal, 1219 5187 LGI family, member 3 Hypothetical protein Contig46563_RC Transcribed 1220 5188 sequences Contig46567 Transcribed 1221 5189 sequences Contig46586 UBE2D3 ubiquitin-conjugating Hypothetical protein, Ligase, Ubl 1222 5190 enzyme E2D 3 conjugation pathway, Multigene (UBC4/5 homolog, family yeast) Contig46590 RAD50 CDNA FLJ46914 fis, Hypothetical protein 1223 5191 clone SPLEN2027852 Contig46591_RC hypothetical protein 1224 5192 LOC90639 Contig46601_RC CDNA FLJ42198 fis, 1225 5193 clone THYMU2034338 Contig46602_RC zinc finger, CCHC Hypothetical protein 1226 5194 domain containing 6 Contig46634 Transcribed 1227 5195 sequences Contig46700_RC LSP1 small proline rich Phosphorylation, T-cell 1228 5196 protein 4 Contig46709_RC FLJ23045 chromosome 20 Transport, Protein transport, 1229 5197 open reading frame Hypothetical protein 23 Contig46732_RC zinc finger protein Hypothetical protein, Zinc-finger, 1230 5198 207 Metal-binding, DNA-binding, Nuclear protein, Alternative splicing Contig46747_RC parvin, gamma Cell adhesion, Cytoskeleton, Actin- 1231 5199 binding, Repeat, Alternative splicing Contig46860_RC FLJ20758 protein Hypothetical protein 1232 5200 Contig46881_RC Transcribed 1233 5201 sequences Contig46954_RC PNMA3 paraneoplastic Hypothetical protein 1234 5202 antigen MA3 Contig46999_RC CDNA FLJ26950 fis, 1235 5203 clone RCT08544 Contig47014_RC MGC24180 hypothetical protein Hypothetical protein 1236 5204 MGC24180 Contig47015_RC hypothetical protein Hypothetical protein 1237 5205 FLJ21439 Contig47025_RC Hypothetical gene 1238 5206 supported by AK094796 (LOC400764), mRNA Contig47042 FLJ20069 Abelson helper Hypothetical protein, Repeat, SH3 1239 5207 integration site domain, WD repeat Contig47081_RC LOC392751 1240 5208 (LOC392751), mRNA Contig47096_RC PFKFB4 6-phosphofructo-2- Multifunctional enzyme, Transferase, 1241 5209 kinase/fructose-2,6- Kinase, Hydrolase, ATP-binding, biphosphatase 4 Phosphorylation, Multigene family, 3D-structure Contig47184_RC LOC400813 1242 5210 (LOC400813), mRNA Contig47203_RC sortilin-related Endocytosis, Receptor, 1243 5211 receptor, L(DLR Transmembrane, EGF-like domain, class) A repeats- Repeat, Glycoprotein, LDL, Lipid containing transport, Cholesterol metabolism, Signal Contig47221_RC VCP valosin-containing ATP-binding, Transport, 1244 5212 protein Phosphorylation, Repeat, Golgi stack, Endoplasmic reticulum, Hypothetical protein Contig47368_RC LOC92691 hypothetical protein Hypothetical protein 1245 5213 BC008604 Contig47441_RC ubiquitin-conjugating Ligase, Ubl conjugation pathway, 1246 5214 enzyme E2 variant 2 Vitamin D Contig47464_RC ZNF335 zinc finger protein Transcription regulation, Zinc-finger, 1247 5215 335 Metal-binding, Nuclear protein, DNA- binding, Repeat Contig47495_RC IDI2 GTP binding protein 4 GTP-binding, Nuclear protein 1248 5216 Contig47498_RC TMPRSS5 transmembrane Hydrolase, Serine protease, 1249 5217 protease, serine 5 Transmembrane, Signal-anchor, (spinesin) Glycoprotein Contig47539_RC SGT1, suppressor of Ubl conjugation pathway, Repeat, 1250 5218 G2 allele of SKP1 TPR repeat (S. cerevisiae) Contig47582_RC FLJ22757 family with sequence Hypothetical protein 1251 5219 similarity 31, member C Contig47732_RC EPS8R3 EPS8-like 3 SH3 domain, Hypothetical protein, 1252 5220 Receptor Contig47770_RC LY6G6C lymphocyte antigen Signal 1253 5221 6 complex, locus G6C Contig47793_RC FLJ23311 FLJ23311 protein Hypothetical protein 1254 5222 Contig47801_RC CDNA FLJ45814 fis, 1255 5223 clone NT2RP7018126 Contig47810_RC IMMP2L IMP2 inner Coated pits 1256 5224 mitochondrial membrane protease- like (S. cerevisiae) Contig47814_RC HHGP phosphoribosyl Transferase 1257 5225 transferase domain containing 1 Contig47835_RC similar to RIKEN Hypothetical protein 1258 5226 cDNA 2600017H02 Contig47863_RC FLJ11939 latrophilin 1 Hypothetical protein, Receptor, 1259 5227 Transmembrane Contig47889_RC COPS7B COP9 constitutive Hypothetical protein 1260 5228 photomorphogenic homolog subunit 7B (Arabidopsis) Contig47900_RC FLJ12604 hypothetical protein Hypothetical protein 1261 5229 FLJ12604 Contig47912_RC NR1D2 nuclear receptor Hypothetical protein, Receptor, 1262 5230 subfamily 1, group Transcription regulation, DNA- D, member 2 binding, Nuclear protein, Zinc-finger, Repressor Contig47922_RC BRAP BRCA1 associated Metal-binding, Zinc, Zinc-finger 1263 5231 protein Contig47926_RC FLJ13057 germ cell-less Hypothetical protein 1264 5232 homolog 1 (Drosophila) Contig47942_RC LOC91893 hypothetical protein Hypothetical protein 1265 5233 BC006136 Contig47975_RC CDNA clone 1266 5234 IMAGE: 5757380, partial cds Contig47982_RC hypothetical protein 1267 5235 LOC112868 Contig48059 FLJ12788 hypothetical protein Hypothetical protein 1268 5236 FLJ12788 Contig48144_RC FLJ11152 chromosome 6 open Hypothetical protein 1269 5237 reading frame 70 Contig48156_RC proprotein Cholesterol metabolism, Lipid 1270 5238 convertase metabolism, Hydrolase, Protease, subtilisin/kexin type 9 Serine protease, Calcium, Signal, Autocatalytic cleavage, Zymogen, Glycoprotein, Alternative splicing, Polymorphism, Disease mutation Contig48168_RC LOC113246 CDNA FLJ46484 fis, Hypothetical protein 1271 5239 clone THYMU3026350 Contig48215_RC FLJ35801 hypothetical protein Hypothetical protein 1272 5240 FLJ35801 Contig48249_RC FLJ10849 hypothetical protein Hypothetical protein 1273 5241 FLJ10849 Contig48270_RC LOC144097 hypothetical protein Hypothetical protein 1274 5242 BC007540 Contig48277_RC FLJ36175 hypothetical protein Repeat, WD repeat, Hypothetical 1275 5243 FLJ36175 protein Contig48290_RC MN7 CDNA FLJ43285 fis, Hypothetical protein 1276 5244 clone MESAN2000067 Contig48355_RC methionine 1277 5245 aminopeptidase 1D Contig48371 malate Oxidoreductase, Tricarboxylic acid 1278 5246 dehydrogenase 1, cycle, NAD NAD (soluble) Contig48406_RC chromosome 12 Hypothetical protein 1279 5247 open reading frame 6 Contig48466_RC FLJ12649 hypothetical protein Hypothetical protein 1280 5248 FLJ12649 Contig48472_RC MAD3 MAX dimerization Hypothetical protein 1281 5249 protein 3 Contig48480_RC ring finger protein 24 Zinc-finger 1282 5250 Contig48489_RC similar to Hypothetical protein 1283 5251 K06A9.1b.p Contig48506_RC KIAA1799 KIAA1799 protein Hypothetical protein 1284 5252 Contig48529_RC CKLFSF2 chemokine-like Chemotaxis, Cytokine, 1285 5253 factor super family 2 Transmembrane Contig48588_RC KIAA1706 KIAA1706 protein Hypothetical protein 1286 5254 Contig48697_RC PFKFB2 6-phosphofructo-2- Multifunctional enzyme, Transferase, 1287 5255 kinase/fructose-2,6- Kinase, Hydrolase, ATP-binding, biphosphatase 2 Phosphorylation, Alternative splicing, Multigene family Contig48722_RC Clone 1288 5256 IMAGE: 5729395, mRNA Contig48764_RC CDNA clone Hypothetical protein 1289 5257 MGC: 71984 IMAGE: 4280819, complete cds Contig48806_RC Similar to RIKEN 1290 5258 cDNA E130012A19 (LOC390789), mRNA Contig48830_RC RPL13 ribosomal protein Ribosomal protein 1291 5259 L13 Contig48834_RC YR-29 KIAA0888 protein Nuclear protein 1292 5260 Contig48914_RC hypothetical protein Hypothetical protein 1293 5261 MGC24133 Contig48944_RC Transcribed 1294 5262 sequences Contig48951_RC chromosome 9 open Hypothetical protein 1295 5263 reading frame 85 Contig48983_RC CDNA FLJ14294 fis, 1296 5264 clone PLACE1008181 Contig48988_RC LOC51099 abhydrolase domain Hypothetical protein 1297 5265 containing 5 Contig49000_RC CDNA FLJ30257 fis, 1298 5266 clone BRACE2002467 Contig49012_RC hypothetical protein Hypothetical protein 1299 5267 DKFZp434J0617 Contig49063_RC A1BG alpha-1-B Hypothetical protein, 1300 5268 glycoprotein Immunoglobulin domain, Glycoprotein, Plasma, Repeat, Signal Contig49169_RC SUV39H2 suppressor of Hypothetical protein, Transferase, 1301 5269 variegation 3-9 Methyltransferase, Chromatin homolog 2 regulator, Nuclear protein, (Drosophila) Alternative splicing Contig49185_RC MGC2744 hypothetical protein Hypothetical protein 1302 5270 MGC2744 Contig49233_RC NRBF-2 nuclear receptor Receptor, Hypothetical protein 1303 5271 binding factor 2 Contig49254_RC RAD53 Homo sapiens, clone Hypothetical protein, ATP-binding, 1304 5272 MGC: 2637 Kinase, Serine/threonine-protein IMAGE: 3505128, kinase, Transferase, Cell cycle, mRNA, complete Phosphorylation, Nuclear protein, cds. Disease mutation, Li-Fraumeni syndrome, 3D-structure Contig49255_RC leucine-rich PPR- Hypothetical protein, Repeat 1305 5273 motif containing Contig49279_RC hypothetical protein Hypothetical protein 1306 5274 FLJ25461 Contig49306_RC DKFZP586K0717 ligand of numb- Zinc-finger, Repeat, Alternative 1307 5275 protein X splicing Contig49344 FLJ22474 growth hormone Hypothetical protein 1308 5276 regulated TBC protein 1 Contig49353_RC MGC41917 zinc finger protein Hypothetical protein, Metal-binding, 1309 5277 550 Nuclear protein, Zinc, Zinc-finger Contig49409 ty82g05.x1 1310 5278 NCI_CGAP_Kid11 Homo sapiens cDNA clone IMAGE: 2285624 3′, mRNA sequence. Contig49468_RC MRNA; cDNA 1311 5279 DKFZp667N1113 (from clone DKFZp667N1113) Contig49509_RC KIAA1673 cytoplasmic Hypothetical protein 1312 5280 polyadenylation element binding protein 4 Contig49522_RC hypothetical protein Hypothetical protein 1313 5281 FLJ13105 Contig49578_RC FLJ20274 xj92d05.x1 Hypothetical protein 1314 5282 Soares_NFL_T_GBC_S1 Homo sapiens cDNA clone IMAGE: 2664681 3′, mRNA sequence. Contig49591_RC activating Hypothetical protein 1315 5283 transcription factor 7 interacting protein 2 Contig49631_RC ATP11C ATPase, Class VI, Hydrolase, Transmembrane, 1316 5284 type 11C Phosphorylation, Magnesium, Metal- binding, ATP-binding, Multigene family, Alternative splicing Contig49667_RC deaminase domain 1317 5285 containing 1 Contig49673_RC AD034 RIO kinase 1 (yeast) Kinase, Hypothetical protein 1318 5286 Contig49725_RC LOC51611 CDNA clone Transferase, Methyltransferase, 1319 5287 IMAGE: 4821863, Alternative splicing, Hypothetical partial cds protein Contig49738_RC ATIC aj25f09.s1 Purine biosynthesis, Transferase, 1320 5288 Soares_testis_NHT Hydrolase, Multifunctional enzyme Homo sapiens cDNA clone 1391369 3′, mRNA sequence. Contig49744_RC FLJ14166 hypothetical protein Hypothetical protein 1321 5289 FLJ14166 Contig49756_RC Transcribed 1322 5290 sequences Contig49849_RC C6orf1 hypothetical protein Hypothetical protein 1323 5291 MGC57858 Contig49855 MGC33338 hypothetical protein Hypothetical protein 1324 5292 MGC33338 Contig49875 Full length insert 1325 5293 cDNA YN61C04 Contig49948_RC MGC27385 potassium channel Hypothetical protein 1326 5294 tetramerisation domain containing 6 Contig49966_RC CDNA FLJ31683 fis, 1327 5295 clone NT2RI2005353 Contig49983_RC MGC3121 hypothetical protein Hypothetical protein 1328 5296 MGC3121 Contig49991_RC Transcribed 1329 5297 sequence with weak similarity to protein ref: NP_062553.1 (H. sapiens) hypothetical protein FLJ11267 [Homo sapiens] Contig50039_RC KIAA0140 similar to CG9643- Hypothetical protein 1330 5298 PA Contig50106_RC KIAA1708 kinesin family Hypothetical protein 1331 5299 member 21A Contig50117_RC Transcribed 1332 5300 sequences Contig50134_RC BITE p10-binding protein Hypothetical protein 1333 5301 Contig50137_RC MGC12992 hypothetical protein GTP-binding, Microtubules, Multigene 1334 5302 MGC12992 family Contig50177_RC MBLR ring finger protein Hypothetical protein, Metal-binding, 1335 5303 134 Zinc, Zinc-finger Contig50190_RC LOC51005 MRNA; cDNA Glycoprotein, Ion transport, Ionic 1336 5304 DKFZp313E2215 channel, Transmembrane (from clone DKFZp313E2215) Contig50194_RC C9orf16 chromosome 9 open Hypothetical protein, Coiled coil 1337 5305 reading frame 16 Contig50211_RC MGC35392 hypothetical protein Hypothetical protein 1338 5306 MGC35392 Contig50220_RC FLJ13231 hypothetical protein Hypothetical protein 1339 5307 FLJ13231 Contig50232_RC DDX31 DEAD (Asp-Glu-Ala- ATP-binding, Helicase, Hydrolase, 1340 5308 Asp) box polypeptide Hypothetical protein 31 Contig50249_RC MGC23908 similar to RNA Hypothetical protein 1341 5309 polymerase B transcription factor 3 Contig50272_RC Transcribed 1342 5310 sequences Contig50273_RC hypothetical protein Hypothetical protein 1343 5311 LOC255783 Contig50275_RC gm117 gm117 1344 5312 Contig50293_RC EGFR-RS rhomboid family 1 Hypothetical protein, Receptor 1345 5313 (Drosophila) Contig50295_RC FLJ12541 stimulated by Hypothetical protein 1346 5314 retinoic acid gene 6 Contig50298_RC FLJ32370 hypothetical protein Hypothetical protein 1347 5315 FLJ32370 Contig50324_RC LOC51044 CDNA FLJ25011 fis, 1348 5316 clone CBL01244 Contig50337_RC MGC4645 hypothetical protein Hypothetical protein, Repeat, WD 1349 5317 MGC4645 repeat Contig50381_RC CD109 CD109 antigen (Gov Hypothetical protein 1350 5318 platelet alloantigens) Contig50391_RC Transcribed 1351 5319 sequence with moderate similarity to protein ref: NP_060312.1 (H. sapiens) hypothetical protein FLJ20489 [Homo sapiens] Contig50436_RC CDNA FLJ37094 fis, 1352 5320 clone BRACE2018337 Contig50465_RC Transcribed 1353 5321 sequences Contig50483 KIAA1718 KIAA1718 protein Hypothetical protein 1354 5322 Contig50490_RC LOC90678 leucine rich repeat Hypothetical protein 1355 5323 and sterile alpha motif containing 1 Contig50501_RC coronin, actin Actin-binding, Repeat, WD repeat, 1356 5324 binding protein, 2A Coiled coil Contig50595_RC hypothetical protein Hypothetical protein 1357 5325 LOC147111 Contig50605_RC wj49g02.x1 1358 5326 NCI_CGAP_Lu19 Homo sapiens cDNA clone IMAGE: 2406194 3′, mRNA sequence. Contig50669_RC KIF9 kinesin family Hypothetical protein, Motor protein, 1359 5327 member 9 Microtubule, ATP-binding, Coiled coil, Alternative splicing Contig50675 BA108L7.2 similar to rat Hypothetical protein, Transport, Iron 1360 5328 tricarboxylate transport, Mitochondrion, carrier-like protein Transmembrane Contig50687_RC MINA53 hypothetical protein Hypothetical protein 1361 5329 DKFZp667G2110 Contig506_RC KIAA1821 rab11-family Hypothetical protein 1362 5330 interacting protein 4 Contig50728_RC Transcribed 1363 5331 sequence with weak similarity to protein ref: NP_071385.1 (H. sapiens) hypothetical protein FLJ20958 [Homo sapiens] Contig50747_RC MGC23427 BTB (POZ) domain 1364 5332 containing 14A Contig50759 DKFZp761P1121 hypothetical protein Hypothetical protein, RNA-binding, 1365 5333 DKFZp761P1121 Repeat, Alternative splicing Contig50787_RC FLJ31528 hypothetical protein Hypothetical protein 1366 5334 FLJ31528 Contig50814_RC MGC27027 immune associated Hypothetical protein 1367 5335 nucleotide Contig50831_RC LOC389865 1368 5336 (LOC389865), mRNA Contig50838_RC LOC120224 hypothetical protein Hypothetical protein 1369 5337 BC016153 Contig50846_RC zinc finger CCCH Hypothetical protein 1370 5338 type domain containing 5 Contig50848_RC KIAA1705 DDHD domain Lipid degradation, Hydrolase, 1371 5339 containing 1 Alternative splicing Contig50891_RC Homo sapiens, ATP-binding, Kinase, 1372 5340 p21/Cdc42/Rac1- Serine/threonine-protein kinase, activated kinase 1 Transferase, Apoptosis, (STE20 homolog, Phosphorylation, 3D-structure yeast), clone MGC: 51883 IMAGE: 5763796, mRNA, complete cds. Contig50905_RC CDNA FLJ42250 fis, 1373 5341 clone TKIDN2007828 Contig50920_RC KIAA1847 Homo sapiens Hypothetical protein, Zinc-finger, 1374 5342 mRNA for KIAA1847 Alternative splicing protein, partial cds. Contig51020_RC MGC21874 transcriptional Hypothetical protein 1375 5343 adaptor 2 (ADA2 homolog, yeast)- beta Contig51026_RC DKFZp762A2013 quiescin Q6-like 1 Hypothetical protein, Signal 1376 5344 Contig51068_RC CDNA clone 1377 5345 IMAGE: 5286843, partial cds Contig51070_RC FLJ25005 FLJ25005 protein Hypothetical protein 1378 5346 Contig51087_RC NPEPL1 aminopeptidase-like 1 Hydrolase, Aminopeptidase, Zinc, 1379 5347 Manganese, Alternative splicing Contig51103_RC JFC1 NADPH oxidase- Hypothetical protein, Repeat, 1380 5348 related, C2 domain- Alternative splicing containing protein Contig51105_RC Transcribed 1381 5349 sequence with weak similarity to protein ref: NP_062553.1 (H. sapiens) hypothetical protein FLJ11267 [Homo sapiens] Contig51128_RC MGC35182 hypothetical protein Hypothetical protein 1382 5350 MGC35182 Contig51151_RC ASP AKAP-associated 1383 5351 sperm protein Contig51163_RC hypothetical protein Hypothetical protein 1384 5352 MGC45871 Contig51170_RC bruno-like 4, RNA Hypothetical protein 1385 5353 binding protein (Drosophila) Contig51254_RC CLG likely ortholog of Hypothetical protein 1386 5354 mouse common-site lymphoma/leukemia GEF Contig51288_RC NR2C2 nuclear receptor Receptor, Transcription regulation, 1387 5355 subfamily 2, group DNA-binding, Nuclear protein, Zinc- C, member 2 finger Contig51291_RC KIAA1977 KIAA1977 protein Hypothetical protein, ANK repeat, 1388 5356 Repeat Contig51297_RC FLJ33817 hypothetical protein Hypothetical protein, Repeat, WD 1389 5357 FLJ33817 repeat Contig51311_RC KDELC1 KDEL (Lys-Asp-Glu- Hypothetical protein 1390 5358 Leu) containing 1 Contig51373_RC KIAA1688 KIAA1688 protein Repeat 1391 5359 Contig51414_RC FLJ23441 hypothetical protein Hypothetical protein 1392 5360 FLJ23441 Contig51417_RC SHANK3 SH3 and multiple SH3-binding, Coiled coil, 1393 5361 ankyrin repeat Chromosomal translocation domains 3 Contig51449_RC RAB15, member Hypothetical protein, Plasmid 1394 5362 RAS onocogene family Contig51519_RC spastic paraplegia 6 Hypothetical protein 1395 5363 (autosomal dominant) Contig51526_RC RAB39B RAB39B, member GTP-binding, Lipoprotein, 1396 5364 RAS oncogene Prenylation, Transport, Protein family transport Contig51553_RC MGC3200 hypothetical protein Hypothetical protein 1397 5365 MGC3200 Contig51567_RC hypothetical protein Hypothetical protein 1398 5366 MGC33371 Contig51621_RC ubiquitin specific Hypothetical protein, Ubl conjugation 1399 5367 protease 13 pathway, Hydrolase, Thiol protease, (isopeptidase T-3) Multigene family, Repeat Contig51625_RC Clone Hypothetical protein 1400 5368 IMAGE: 3868989, mRNA, partial cds Contig51660_RC IFRG28 28 kD interferon Transmembrane 1401 5369 responsive protein Contig51687_RC KRTDAP KIPV467 1402 5370 Contig51723_RC Splicing factor, 1403 5371 arginine/serine-rich, 46 kD Contig51726_RC FLJ20739 Transcribed Hypothetical protein 1404 5372 sequence with weak similarity to protein pir: S41161 (H. sapiens) S41161 keratin 9, cytoskeletal - human Contig51737_RC CDNA FLJ38931 fis, 1405 5373 clone NT2NE2013189 Contig51740_RC FLJ33282 amyotrophic lateral Hypothetical protein 1406 5374 sclerosis 2 (juvenile) chromosome region, candidate 4 Contig51742_RC RISC likely homolog of rat Hydrolase, Carboxypeptidase, 1407 5375 and mouse retinoid- Signal, Glycoprotein, Alternative inducible serine splicing carboxypeptidase Contig51757 lin-7 homolog A (C. elegans) 1408 5376 Contig51795_RC TGFBI CDNA FLJ37830 fis, Extracellular matrix, Signal, Repeat, 1409 5377 clone Cell adhesion, Disease mutation, BRSSN2009395 Amyloid, Vision Contig51800 Transcribed 1410 5378 sequence with strong similarity to protein pdb: 1BGM (E. coli) O Chain O, Beta-Galactosidase Contig51809_RC C21orf63 chromosome 21 Signal, Transmembrane, Repeat, 1411 5379 open reading frame Glycoprotein, Lectin, Alternative 63 splicing Contig51821_RC TAF4B TAF4b RNA Transcription regulation, Nuclear 1412 5380 polymerase II, TATA protein box binding protein (TBP)-associated factor, 105 kDa Contig51882_RC MGC11335 hypothetical protein Hypothetical protein 1413 5381 MGC11335 Contig51888_RC pannexin 1 Gap junction, Transmembrane, 1414 5382 Polymorphism Contig51896_RC HT021 HT021 1415 5383 Contig51917_RC WBSCR14 Full length insert Transcription regulation, Repressor, 1416 5384 cDNA clone Nuclear protein, DNA-binding, YI46G04 Williams-Beuren syndrome, Alternative splicing Contig51929 PAI-1 mRNA-binding Hypothetical protein 1417 5385 protein Contig51964_RC FLJ40629 hypothetical protein Hypothetical protein 1418 5386 FLJ40629 Contig51967_RC solute carrier family Transport, Symport, 1419 5387 16 (monocarboxylic Transmembrane, Multigene family acid transporters), member 6 Contig51974_RC Transcribed Hypothetical protein, Phospholipid 1420 5388 sequences biosynthesis, Transferase, Acyltransferase, Transmembrane Contig52062_RC FLJ31978 hypothetical protein Hypothetical protein 1421 5389 FLJ31978 Contig52099_RC CDNA FLJ41881 fis, 1422 5390 clone OCBBF2021833 Contig52186_RC zinc finger protein 67 Metal-binding, Zinc, Zinc-finger 1423 5391 homolog (mouse) Contig52199_RC CDNA FLJ12540 fis, 1424 5392 clone NT2RM4000425 Contig52220_RC CDNA FLJ25573 fis, 1425 5393 clone JTH06531 Contig52232_RC DERMO1 twist homolog 2 Differentiation, Developmental 1426 5394 (Drosophila) protein, Nuclear protein, DNA- binding, Repressor, Transcription regulation Contig52242_RC CDNA FLJ12345 fis, Hypothetical protein 1427 5395 clone MAMMA1002294 Contig52312_RC TFEB transcription factor Transcription regulation, DNA- 1428 5396 EB binding, Nuclear protein, Alternative splicing Contig52317_RC hypothetical protein Hypothetical protein, Ubiquinone 1429 5397 LOC91942 Contig52320 Full length insert 1430 5398 cDNA clone YX81F03 Contig52336_RC MGC2488 homolog of yeast Hypothetical protein 1431 5399 Mis12 Contig52358_RC Transcribed 1432 5400 sequences Contig52405_RC EDG3 endothelial G-protein coupled receptor, 1433 5401 differentiation, Transmembrane, Glycoprotein sphingolipid G- protein-coupled receptor, 3 Contig52414_RC CAMTA1 calmodulin binding Hypothetical protein, ANK repeat, 1434 5402 transcription Repeat activator 1 Contig52443 hypothetical protein 1435 5403 INM01 Contig52482_RC PNPASE polyribonucleotide Hypothetical protein, Exonuclease, 1436 5404 nucleotidyltransferase 1 Nucleotidyltransferase, Transferase Contig52486_RC PPARAL CDNA FLJ31089 fis, 1437 5405 clone IMR321000092 Contig52520_RC MRNA full length 1438 5406 insert cDNA clone EUROIMAGE 2068962 Contig52544_RC MGC17515 hypothetical protein Hypothetical protein 1439 5407 MGC17515 Contig52553_RC LOC197336 similar to RIKEN Hypothetical protein, Repeat, WD 1440 5408 cDNA 3230401M21 repeat [Mus musculus] Contig52561_RC Cas-Br-M (murine) Hypothetical protein, Ligase, Ubl 1441 5409 ecotropic retroviral conjugation pathway, Proto- transforming oncogene, Zinc-finger, SH2 domain, sequence Phosphorylation, Calcium-binding, 3D-structure Contig52565_RC MAX dimerization Nuclear protein, DNA-binding, 1442 5410 protein 1 Transcription regulation, Repressor, 3D-structure Contig52570_RC CDNA FLJ41853 fis, 1443 5411 clone NT2RI3004161 Contig52579_RC breast cancer 1444 5412 membrane protein 101 Contig52609_RC hypothetical protein Hypothetical protein 1445 5413 FLJ33814 Contig52623_RC FLJ12888 chromosome 9 open Hypothetical protein 1446 5414 reading frame 76 Contig52648_RC MGC2404 acyl-Coenzyme A ANK repeat, Repeat 1447 5415 binding domain containing 6 Contig52659_RC hypothetical protein Hypothetical protein 1448 5416 LOC255104 Contig52715_RC Transcribed 1449 5417 sequences Contig52720_RC MGC2714 hypothetical protein Hypothetical protein 1450 5418 MGC2714 Contig52729_RC MGC3020 hypothetical protein Hypothetical protein 1451 5419 MGC3020 Contig5274_RC C21orf91 chromosome 21 Polymorphism 1452 5420 open reading frame 91 Contig52777_RC Transcribed 1453 5421 sequence with strong similarity to protein ref: NP_286085.1 (E. coli) beta-D- galactosidase [Escherichia coli O157:H7 EDL933] Contig52786_RC ZNF198 zinc finger protein Hypothetical protein, Transcription 1454 5422 198 regulation, Nuclear protein, Chromosomal translocation, Repeat, Zinc-finger Contig52792_RC MGC3062 phosducin-like 3 1455 5423 Contig52814_RC Transcribed 1456 5424 sequences Contig52891_RC membrane Hypothetical protein 1457 5425 associated guanylate kinase interacting protein- like 1 Contig52914_RC MGC4663 cytochrome P450, Hypothetical protein 1458 5426 family 2, subfamily R, polypeptide 1 Contig52924_RC FLJ14827 hypothetical protein Hypothetical protein 1459 5427 FLJ14827 Contig52932_RC DKFZP566D1346 hypothetical protein Hypothetical protein, ANK repeat, 1460 5428 DKFZp566D1346 Repeat Contig52945_RC KIAA1946 KIAA1946 protein Hypothetical protein 1461 5429 Contig52971_RC SCAMP5 secretory carrier Hypothetical protein 1462 5430 membrane protein 5 Contig52993_RC MAP3K3 mitogen-activated Hypothetical protein, ATP-binding, 1463 5431 protein kinase Transferase, Serine/threonine- kinase kinase 3 protein kinase Contig52994_RC Transcribed 1464 5432 sequence with weak similarity to protein ref: NP_055301.1 (H. sapiens) neuronal thread protein [Homo sapiens] Contig53047_RC TTYH1 tweety homolog 1 1465 5433 (Drosophila) Contig53066_RC ARL5 ADP-ribosylation GTP-binding, Multigene family 1466 5434 factor-like 5 Contig53072_RC KIAA1474 zinc finger protein Hypothetical protein, Metal-binding, 1467 5435 537 Zinc, Zinc-finger Contig53080_RC CDNA FLJ31655 fis, 1468 5436 clone NT2RI2004284 Contig53149_RC RIN3 Ras and Rab GTPase activation, SH2 domain, 1469 5437 interactor 3 Alternative splicing, Plasmid Contig53177_RC CDNA FLJ90571 fis, 1470 5438 clone OVARC1001725, highly similar to Homo sapiens patched related protein TRC8 (TRC8) gene. Contig53211_RC FLJ11588 hypothetical protein Hypothetical protein 1471 5439 FLJ11588 Contig53223 PPP1R15B protein phosphatase Hypothetical protein 1472 5440 1, regulatory (inhibitor) subunit 15B Contig53226_RC hypothetical protein Hypothetical protein 1473 5441 DKFZp762C1112 Contig53243_RC hypothetical protein Hypothetical protein 1474 5442 LOC257106 Contig53253_RC WWP2 Nedd-4-like Ubl conjugation pathway, Ligase, 1475 5443 ubiquitin-protein Repeat ligase Contig53260_RC hypothetical protein Hypothetical protein 1476 5444 LOC196264 Contig53307_RC LOC51184 Homo sapiens Hypothetical protein 1477 5445 mRNA full length insert cDNA clone EUROIMAGE 1635059. Contig53323 KIAA1608 KIAA1608 Hypothetical protein 1478 5446 Contig53342_RC Transcribed 1479 5447 sequences Contig53349_RC FLJ12287 hypothetical protein Hypothetical protein, Signal, 1480 5448 FLJ12287 similar to Transmembrane, Immunoglobulin semaphorins domain, Multigene family, Neurogenesis, Developmental protein, Glycoprotein Contig53355_RC MGC10870 hypothetical protein 1481 5449 MGC10870 Contig53410_RC FLJ14596 chromosome 9 open Hypothetical protein 1482 5450 reading frame 54 Contig53439_RC FLJ22457 hypothetical protein Hypothetical protein 1483 5451 FLJ22457 Contig53460_RC CDNA FLJ30010 fis, 1484 5452 clone 3NB692000154 Contig5348_RC Transcribed 1485 5453 sequence with weak similarity to protein sp: Q13892 (H. sapiens) BT33_HUMAN Transcription factor BTF3 homolog 3 Contig53517_RC PJA1 praja 1 Ubl conjugation pathway, Ligase, 1486 5454 Zinc-finger, Alternative splicing Contig53555_RC myotubularin related Hydrolase, Zinc-finger, Alternative 1487 5455 protein 3 splicing, Hypothetical protein Contig53566_RC LANCL2 LanC lantibiotic Hypothetical protein 1488 5456 synthetase component C-like 2 (bacterial) Contig53585_RC CG005 phosphonoformate Hypothetical protein 1489 5457 immuno-associated protein 5 Contig53615_RC MGC4692 hypothetical protein 1490 5458 LOC283871 Contig53635_RC FLJ39514 sec1 family domain Hypothetical protein 1491 5459 containing 2 Contig53641_RC MAGE-E1 melanoma antigen, Hypothetical protein 1492 5460 family D, 4 Contig53696_RC MDS006 x 006 protein 1493 5461 Contig53709_RC adaptor-related Golgi stack, Protein transport, 1494 5462 protein complex 1, Transport, Coated pits, Endocytosis, gamma 1 subunit Polymorphism, 3D-structure, Hypothetical protein Contig53719_RC FLJ30596 hypothetical protein Hypothetical protein 1495 5463 FLJ30596 Contig53746_RC DRLM nucleosome Hypothetical protein 1496 5464 assembly protein 1- like 5 Contig53819_RC MGC11296 breast cancer 1497 5465 metastasis- suppressor 1-like Contig53823_RC FLJ31295 hypothetical protein Metal-binding, Zinc, Zinc-finger, 1498 5466 FLJ31295 Hypothetical protein Contig53829 MGC3123 hypothetical protein Hypothetical protein 1499 5467 MGC3123 Contig53852_RC KIAA1577 zinc finger, SWIM Hypothetical protein 1500 5468 domain containing 6 Contig53884_RC LOC59346 PDZ and LIM Hypothetical protein, LIM domain, 1501 5469 domain 2 (mystique) Metal-binding, Zinc Contig53909_RC MGC23947 hypothetical protein Hypothetical protein 1502 5470 MGC23947 Contig5392_RC Transcribed 1503 5471 sequences Contig53944_RC MI-ER1 putative NFkB Hypothetical protein 1504 5472 activating protein 373 Contig53985_RC FLJ30596 hypothetical protein Hypothetical protein 1505 5473 FLJ30596 Contig54010_RC MDS024 chromosome 6 open 1506 5474 reading frame 75 Contig54012_RC SAS10 MRNA; cDNA Hypothetical protein 1507 5475 DKFZp686C2051 (from clone DKFZp686C2051) Contig54048_RC GC1 solute carrier family Mitochondrion, Inner membrane, 1508 5476 25 (mitochondrial Repeat, Transmembrane, Transport, carrier: glutamate), Symport member 22 Contig54066_RC DEDD2 death effector DNA-binding, Hypothetical protein 1509 5477 domain containing 2 Contig54110_RC splicing factor, mRNA processing, mRNA splicing, 1510 5478 arginine/serine-rich 1 Nuclear protein, RNA-binding, (splicing factor 2, Repeat, Alternative splicing, alternate splicing Acetylation, Phosphorylation factor) Contig54113_RC FLJ11785 Rad50-interacting Hypothetical protein 1511 5479 protein 1 Contig54137_RC zinc finger protein 84 Transcription regulation, DNA- 1512 5480 (HPF2) binding, Zinc-finger, Metal-binding, Nuclear protein, Repeat Contig54184_RC MGC955 hypothetical protein Hypothetical protein 1513 5481 MGC955 Contig54317_RC MGC29956 hypothetical protein Hypothetical protein 1514 5482 MGC29956 Contig54321_RC DDX33 DEAH (Asp-Glu-Ala- Hypothetical protein, ATP-binding, 1515 5483 His) box polypeptide Helicase, Hydrolase 33 Contig54342_RC MGC13096 hypothetical protein Cytokine, Disease 1516 5484 MGC13096 mutation, Gluconeogenesis, Glycolysis, Growth factor, Isomerase, Neurone Contig54371_RC GKAP42 protein kinase Hypothetical protein, Kinase 1517 5485 anchoring protein GKAP42 Contig54463_RC CDNA FLJ12874 fis, 1518 5486 clone NT2RP2003769 Contig54503_RC kelch-like 11 Hypothetical protein 1519 5487 (Drosophila) Contig54531_RC Homo sapiens cDNA 1520 5488 FLJ38849 fis, clone MESAN2008936. Contig54559_RC ankyrin repeat and ANK repeat, Repeat 1521 5489 BTB (POZ) domain containing 1 Contig54563_RC KNSL5 kinesin family Motor protein, Cell division, 1522 5490 member 23 Microtubule, ATP-binding, Coiled coil, Mitosis, Cell cycle, Nuclear protein Contig54581_RC tumor suppressor 1523 5491 TSBF1 Contig54609_RC PANK3 pantothenate kinase 3 Transferase, Kinase, ATP-binding, 1524 5492 Coenzyme A biosynthesis Contig54614_RC FLJ14007 hypothetical protein Hypothetical protein 1525 5493 FLJ14007 Contig54659_RC HCCA2 HCCA2 protein Hypothetical protein 1526 5494 Contig54667_RC ERAP140 nuclear receptor Receptor, Hypothetical protein 1527 5495 coactivator 7 Contig54680_RC nucleotide-binding Hypothetical protein 1528 5496 oligomerization domains 27 Contig54686_RC zinc finger protein Hypothetical protein 1529 5497 598 Contig54716_RC KIAA0863 KIAA0863 protein Hypothetical protein, Metal-binding, 1530 5498 Zinc, Zinc-finger Contig54718_RC FLJ37562 hypothetical protein Hypothetical protein 1531 5499 FLJ37562 Contig54729_RC chromosome 10 Hypothetical protein 1532 5500 open reading frame 30 Contig54751_RC VIK vav-1 interacting Metal-binding, Zinc, Zinc-finger, 1533 5501 Kruppel-like protein Hypothetical protein Contig54757_RC hypothetical protein Hypothetical protein 1534 5502 LOC129293 Contig54802_RC GPR108 G protein-coupled Hypothetical protein 1535 5503 receptor 108 Contig54829_RC TJP3 tight junction protein Hypothetical protein 1536 5504 3 (zona occludens 3) Contig54893_RC APOBEC3G apolipoprotein B Hypothetical protein 1537 5505 mRNA editing enzyme, catalytic polypeptide-like 3G Contig54915_RC DR1 Hypothetical gene Transcription, Phosphorylation, 1538 5506 supported by Nuclear protein, 3D-structure AL832786 (LOC400762), mRNA Contig54932_RC BIVM basic, Hypothetical protein 1539 5507 immunoglobulin-like variable motif containing Contig54961_RC lemur tyrosine Hypothetical protein, ATP-binding, 1540 5508 kinase 2 Kinase, Transferase, Tyrosine- protein kinase Contig5498_RC C17orf26 solute carrier family Hypothetical protein 1541 5509 39 (metal ion transporter), member 11 Contig54999_RC FLJ12994 hypothetical protein Hypothetical protein 1542 5510 FLJ12994 Contig55004 DKFZP564O0463 mitochondrial folate Mitochondrion, Inner membrane, 1543 5511 transporter/carrier Repeat, Transmembrane, Transport Contig55022_RC ALP asparaginase like 1 Hypothetical protein 1544 5512 Contig55038_RC MCOLN1 mucolipin 1 Ionic channel, Transmembrane, 1545 5513 Hypothetical protein Contig55044_RC DECR2 2,4-dienoyl CoA Oxidoreductase, Hypothetical protein 1546 5514 reductase 2, peroxisomal Contig55069_RC Hypothetical gene 1547 5515 supported by BC040598 (LOC400960), mRNA Contig55079_RC FLJ21613 corneal wound Hypothetical protein 1548 5516 healing-related protein Contig55114_RC chromosome 6 open Hypothetical protein 1549 5517 reading frame 89 Contig55121_RC P5326 hypothetical protein Hypothetical protein 1550 5518 p5326 Contig5513_RC Transcribed 1551 5519 sequences Contig55181_RC LOC115509 hypothetical protein Hypothetical protein, Metal-binding, 1552 5520 BC014000 Zinc, Zinc-finger Contig55193_RC HS6ST1 heparan sulfate 6-O- Transferase 1553 5521 sulfotransferase 1 Contig55254_RC LOC220074 Hypothetical 55.1 kDa 1554 5522 protein F09G8.5 in chromosome III Contig55265_RC ets variant gene 6 Transcription regulation, Repressor, 1555 5523 (TEL oncogene) Nuclear protein, DNA-binding, Phosphorylation, Proto-oncogene, Chromosomal translocation, 3D- structure Contig55334_RC DKFZp547C195 hypothetical protein Hypothetical protein 1556 5524 DKFZp547C195 Contig55337_RC MGC2454 chromosome 2 open Hypothetical protein, 1557 5525 reading frame 8 Methyltransferase, Transferase Contig55351_RC hypothetical protein Hypothetical protein 1558 5526 MGC45871 Contig55365_RC CDNA clone 1559 5527 IMAGE: 6702802, partial cds Contig55375_RC C1QTNF6 C1q and tumor Collagen, Signal 1560 5528 necrosis factor related protein 6 Contig55377_RC DKFZp761H0421 RUN domain Hypothetical protein 1561 5529 containing 1 Contig55397_RC CSPG6 sterile alpha motif Hypothetical protein, ANK repeat, 1562 5530 domain containing 6 Repeat Contig55468_RC solute carrier family Hypothetical protein 1563 5531 9 (sodium/hydrogen exchanger), isoform 9 Contig55487_RC solute carrier family Hypothetical protein 1564 5532 39 (zinc transporter), member 10 Contig55522 LOC400236 1565 5533 (LOC400236), mRNA Contig55539_RC GAAI470 Hypothetical protein 1566 5534 Contig55574_RC KIAA1940 KIAA1940 protein Hypothetical protein 1567 5535 Contig55575_RC SDS3 likely ortholog of Hypothetical protein 1568 5536 mouse Sds3 Contig55618_RC MGC4825 hypothetical protein Hypothetical protein 1569 5537 MGC4825 Contig55671_RC nuclear factor of Transcription regulation, Activator, 1570 5538 activated T-cells, Nuclear protein, DNA-binding, cytoplasmic, Alternative splicing, Phosphorylation, calcineurin- Repeat, 3D-structure dependent 2 Contig55674_RC DUSP16 LOC387840 Hydrolase, Nuclear protein, 1571 5539 (LOC387840), Hypothetical protein mRNA Contig55709_RC chromosome 14 1572 5540 open reading frame 35 Contig55712_RC hypothetical protein Hypothetical protein 1573 5541 LOC286257 Contig55744_RC DIRC2 disrupted in renal Hypothetical protein 1574 5542 carcinoma 2 Contig55759_RC hypothetical protein Repeat, ANK repeat, Alternative 1575 5543 LOC145758 splicing Contig55766_RC TOMM70A hypothetical protein Mitochondrion, Outer membrane, 1576 5544 LOC348801 Transmembrane, Repeat, TPR repeat Contig55767_RC FLJ22662 hypothetical protein Hypothetical protein 1577 5545 FLJ22662 Contig55814_RC protein containing 1578 5546 single MORN motif in testis Contig55886_RC zinc finger protein 1579 5547 181 (HHZ181) Contig55940_RC MGC13010 hypothetical protein Hypothetical protein 1580 5548 MGC13010 Contig55944_RC FLJ20958 MRNA; cDNA Hypothetical protein 1581 5549 DKFZp686A1197 (from clone DKFZp686A1197) Contig55950_RC FLJ22329 hypothetical protein Hypothetical protein 1582 5550 FLJ22329 Contig55966_RC DKFZP762N2316 zinc finger protein Hypothetical protein, Metal-binding, 1583 5551 462 Zinc, Zinc-finger Contig55979_RC MGC14136 chromosome 21 Hypothetical protein 1584 5552 open reading frame 119 Contig55_RC protein kinase, AMP- Fatty acid biosynthesis, 1585 5553 activated, beta 2 Phosphorylation non-catalytic subunit Contig56036_RC CD47 CD47 antigen (Rh- Integrin, Cell adhesion, Antigen, 1586 5554 related antigen, Signal, Transmembrane, integrin-associated Glycoprotein, Alternative splicing signal transducer) Contig56052_RC hypothetical protein 1587 5555 LOC203547 Contig56056_RC TRUB1 TruB pseudouridine 1588 5556 (psi) synthase homolog 1 (E. coli) Contig56061_RC DEF6 differentially 1589 5557 expressed in FDCP 6 homolog (mouse) Contig56082_RC RNU2 Homo sapiens Hypothetical protein 1590 5558 mRNA; cDNA DKFZp666D074 (from clone DKFZp666D074). Contig56147_RC hypothetical protein Hypothetical protein 1591 5559 LOC338799 Contig56167_RC BAALC brain and acute Hypothetical protein 1592 5560 leukemia, cytoplasmic Contig56179_RC MGC15523 hypothetical protein Hypothetical protein 1593 5561 MGC15523 Contig56229 likely ortholog of Hypothetical protein 1594 5562 mouse zinc finger protein EZI Contig56234_RC IMAGE3451454 SVAP1 protein Hypothetical protein 1595 5563 Contig56242_RC FLJ23221 hypothetical protein Hypothetical protein 1596 5564 FLJ23221 Contig56253_RC FLJ21087 brix domain Nuclear protein 1597 5565 containing 1 Contig56263_RC FLJ21080 SET and MYND Zinc-finger, Hypothetical protein 1598 5566 domain containing 3 Contig56298_RC FLJ13154 hypothetical protein Hypothetical protein 1599 5567 FLJ13154 Contig56303_RC LOC51112 v-abl Abelson Transferase, Tyrosine-protein 1600 5568 murine leukemia kinase, Proto-oncogene, ATP- viral oncogene binding, Phosphorylation, SH2 homolog 2 (arg, domain, SH3 domain, Alternative Abelson-related splicing gene) Contig56334_RC RAI16 retinoic acid induced Hypothetical protein 1601 5569 16 Contig56350_RC MGC4607 cerebral cavernous Hypothetical protein 1602 5570 malformation 2 Contig56390_RC MGC26847 sushi domain 1603 5571 containing 3 Contig56395_RC FLJ14624 hypothetical protein Hypothetical protein 1604 5572 FLJ14624 Contig5639_RC phosphorylase, Transferase, Glycosyltransferase, 1605 5573 glycogen; liver (Hers Carbohydrate metabolism, Glycogen disease, glycogen metabolism, Allosteric enzyme, storage disease type Pyridoxal phosphate, VI) Phosphorylation, Glycogen storage disease, Disease mutation, Polymorphism, 3D-structure Contig56503_RC MGC9753 CAB2 protein Hypothetical protein 1606 5574 Contig56527_RC FLJ20758 protein Hypothetical protein 1607 5575 Contig56541_RC LSFR2 dolichyl 1608 5576 pyrophosphate phosphatase 1 Contig56544_RC H3F3A hypothetical protein Nuclear protein, Chromosomal 1609 5577 FLJ20403 protein, DNA-binding, Nucleosome core, Multigene family Contig56572_RC DKFZP564B1162 hypothetical protein Hypothetical protein 1610 5578 DKFZp564B1162 Contig56583_RC PF20 PF20 Repeat, WD repeat, Hypothetical 1611 5579 protein Contig56587_RC HDAC10 histone deacetylase Hydrolase, Nuclear protein, 1612 5580 10 Chromatin regulator, Transcription regulation, Repressor, Polymorphism, Alternative splicing Contig565_RC CDNA FLJ31683 fis, 1613 5581 clone NT2RI2005353 Contig56623_RC Cas-Br-M (murine) Hypothetical protein, Ligase, Ubl 1614 5582 ecotropic retroviral conjugation pathway, Proto- transforming oncogene, Zinc-finger, SH2 domain, sequence Phosphorylation, Calcium-binding, 3D-structure Contig56662_RC MGC10963 THAP domain Zinc-finger, DNA-binding 1615 5583 containing 7 Contig56671_RC FLJ12761 mSin3A-associated Hypothetical protein 1616 5584 protein 130 Contig56716_RC KIAA1754 KIAA1754 Hypothetical protein 1617 5585 Contig56735_RC CDNA FLJ90790 fis, Hypothetical protein 1618 5586 clone THYRO1001529, weakly similar to SERINE PALMITOYLTRANSFERASE 2 (EC 2.3.1.50). Contig56781_RC MGC11349 hypothetical protein Hypothetical protein, Metal-binding, 1619 5587 MGC11349 Zinc, Zinc-finger Contig56823_RC Transcribed 1620 5588 sequence with moderate similarity to protein ref: NP_060265.1 (H. sapiens) hypothetical protein FLJ20378 [Homo sapiens] Contig56944_RC ASH1 ash1 (absent, small, Hypothetical protein 1621 5589 or homeotic)-like (Drosophila) Contig57011_RC CDA11 CDA11 protein Hypothetical protein 1622 5590 Contig57017_RC TFB2M transcription factor Hypothetical protein 1623 5591 B2, mitochondrial Contig57036_RC hypothetical protein Fatty acid biosynthesis, Biotin, 1624 5592 LOC283445 Ligase, Multifunctional enzyme, ATP-binding, Phosphorylation, Alternative splicing Contig57057_RC MAP3K3 hypothetical protein Hypothetical protein, LIM domain, 1625 5593 MGC10986 Metal-binding, Zinc Contig57076_RC FBXO32 F-box only protein Ubl conjugation pathway 1626 5594 32 Contig57081_RC MSI2 musashi homolog 2 Hypothetical protein 1627 5595 (Drosophila) Contig57090_RC Full length insert 1628 5596 cDNA clone YZ93G08 Contig5716_RC CDNA FLJ38396 fis, 1629 5597 clone FEBRA2007957 Contig57173_RC KIAA1737 KIAA1737 Hypothetical protein 1630 5598 Contig571_RC ST6GALNAC6 CMP-NeuAC: (beta)- Glycosyltransferase, Transferase, 1631 5599 N- Hypothetical protein acetylgalactosaminide (alpha)2,6- sialyltransferase member VI Contig57226_RC tubulin, beta, 2 GTP-binding, Hypothetical protein, 1632 5600 Microtubule, Multigene family Contig57239_RC EPI64 KIAA0114 gene Hypothetical protein 1633 5601 product Contig57270_RC ABCC4 ATP-binding ATP-binding, Glycoprotein, 1634 5602 cassette, sub-family Transmembrane, Transport, Repeat C (CFTR/MRP), member 4 Contig57290_RC hypothetical protein 1635 5603 LOC286334 Contig57417 LOC80298 transcription Hypothetical protein 1636 5604 termination factor- like protein Contig57436_RC PPP2R5E protein phosphatase Phosphorylation, Multigene family 1637 5605 2, regulatory subunit B (B56), epsilon isoform Contig57458_RC IL6R interleukin 6 receptor Receptor, Transmembrane, 1638 5606 Glycoprotein, Immunoglobulin domain, Repeat, Alternative splicing, Signal, 3D-structure Contig57493_RC MGC4399 mitochondrial carrier 1639 5607 protein Contig57562_RC M11S1 membrane GPI-anchor 1640 5608 component, chromosome 11, surface marker 1 Contig57579 ABTB1 ankyrin repeat and ANK repeat, Repeat 1641 5609 BTB (POZ) domain containing 1 Contig57625_RC FLJ14225 polycystic kidney Hypothetical protein 1642 5610 disease 1-like Contig57822_RC CDNA clone 1643 5611 IMAGE: 5286019, partial cds Contig57825_RC MGC18216 hypothetical protein Hypothetical protein 1644 5612 MGC18216 Contig57840_RC MBP CDNA clone Hypothetical protein, Myelin, 1645 5613 MGC: 70813 Structural protein, Acetylation, IMAGE: 6060520, Methylation, Phosphorylation, complete cds Citrullination, Autoimmune encephalomyelitis, 3D-structure, Alternative splicing Contig57957_RC COL5A2 similar to RIKEN Hypothetical protein 1646 5614 cDNA 5730578N08 gene Contig58042_RC CDNA FLJ39602 fis, 1647 5615 clone SKNSH2005061 Contig58113_RC FLJ14005 hypothetical protein Hypothetical protein 1648 5616 LOC286044 Contig58123_RC NFYB nuclear transcription Transcription regulation, DNA- 1649 5617 factor Y, beta binding, Activator, Nuclear protein, 3D-structure Contig58145_RC YEA solute carrier family Hypothetical protein 1650 5618 35, member B4 Contig58156_RC C20orf167 deoxynucleotidyltransferase, Nuclear protein, Polymorphism 1651 5619 terminal, interacting protein 1 Contig58193_RC TCF7L2 transcription factor Transcription regulation, Activator, 1652 5620 7-like 2 (T-cell Repressor, Trans-acting factor, specific, HMG-box) Nuclear protein, DNA-binding, Wnt signaling pathway, Alternative splicing, 3D-structure, Hypothetical protein Contig58213_RC PPARBP PPAR binding DNA-binding, Transcription 1653 5621 protein regulation, Activator, Repeat, Nuclear protein, Alternative splicing Contig58249_RC moblak MOB1, Mps One Hypothetical protein 1654 5622 Binder kinase activator-like 2A (yeast) Contig58260_RC DGAT2 diacylglycerol O- Hypothetical protein, 1655 5623 acyltransferase Acyltransferase, Transferase homolog 2 (mouse) Contig58275_RC general transcription 1656 5624 factor IIIC, polypeptide 4, 90 kDa Contig58288_RC LOC89941 ras homolog gene Hypothetical protein, GTP-binding 1657 5625 family, member T2 Contig58339_RC FLJ21616 MRNA; cDNA Hypothetical protein 1658 5626 DKFZp686E1648 (from clone DKFZp686E1648) Contig58353_RC FLJ13089 hypothetical protein Hypothetical protein 1659 5627 FLJ13089 Contig58491_RC TRIP11 ah24a06.s1 Hypothetical protein, Antigen, Golgi 1660 5628 Soares_parathyroid_tumor_NbHPA stack, Coiled coil, Chromosomal Homo sapiens cDNA translocation clone 1239730 3′, mRNA sequence. Contig58530_RC KIAA1560 glycerol 3-phosphate Hypothetical protein, Phospholipid 1661 5629 acyltransferase, biosynthesis, Transferase, mitochondrial Acyltransferase, Transmembrane, Mitochondrion, Transit peptide Contig58595_RC AP1M1 adaptor-related Golgi stack, Protein transport, 1662 5630 protein complex 1, Transport, Coated pits, Endocytosis, mu 1 subunit Phosphorylation Contig58613 VPS4B vacuolar protein ATP-binding 1663 5631 sorting 4B (yeast) Contig58966_RC HLA-F major MHC 1664 5632 histocompatibility complex, class I, F Contig59120_RC FLJ37080 adhesion molecule Hypothetical protein 1665 5633 AMICA Contig59127_RC PCF11 pre-mRNA cleavage mRNA processing, Nuclear protein 1666 5634 complex II protein Pcf11 Contig59134_RC hypothetical protein 1667 5635 LOC283481 Contig59136_RC qp75d05.x1 1668 5636 Soares_fetal_lung_N bHL19W Homo sapiens cDNA clone IMAGE: 1928841 3′ similar to gb: D14531 60S RIBOSOMAL PROTEIN L9 (HUMAN); mRNA sequence. Contig59187_RC NUDT3 nudix (nucleoside Hydrolase 1669 5637 diphosphate linked moiety X)-type motif 3 Contig5954_RC similar to RIKEN Hypothetical protein, Iron, Iron-sulfur 1670 5638 cDNA B230118G17 gene Contig60075 FLJ32468 ESTs 1671 5639 Contig60315_RC MGC39807 organic solute Hypothetical protein 1672 5640 transporter alpha Contig6041_RC Transcribed 1673 5641 sequences Contig60509_RC GL004 protein Hypothetical protein 1674 5642 Contig60612_RC xylosyltransferase I Transferase, Glycosyltransferase 1675 5643 Contig6064_RC Colorectal cancer- 1676 5644 related mRNA sequence Contig60981_RC p10-binding protein Hypothetical protein 1677 5645 Contig61061_RC RASGRP4 RAS guanyl Hypothetical protein 1678 5646 releasing protein 4 Contig6113_RC CDNA FLJ30090 fis, 1679 5647 clone BNGH41000015 Contig61227_RC hypothetical protein Hypothetical protein, Repeat, WD 1680 5648 FLJ10055 repeat Contig61254_RC MGC5352 hypothetical protein Hypothetical protein 1681 5649 MGC5352 Contig61264_RC KIAA1833 hypothetical protein Hypothetical protein 1682 5650 KIAA1833 Contig61267_RC C20orf126 chromosome 20 Hypothetical protein 1683 5651 open reading frame 126 Contig61815 LOC51063 hypothetical protein Hypothetical protein 1684 5652 LOC51063 Contig61848_RC Transcribed 1685 5653 sequence with weak similarity to protein ref: NP_060312.1 (H. sapiens) hypothetical protein FLJ20489 [Homo sapiens] Contig61915_RC MGC2803 hypothetical protein Hypothetical protein 1686 5654 MGC2803 Contig61975 MGC11242 hypothetical protein Hypothetical protein 1687 5655 MGC11242 Contig62149_RC chromosome 22 Hypothetical protein 1688 5656 open reading frame 23 Contig6254_RC Transcribed 1689 5657 sequences Contig62568_RC MRPL24 mitochondrial Ribosomal protein, Hypothetical 1690 5658 ribosomal protein protein L24 Contig62588_RC hypothetical protein DNA-binding, Metal-binding, Nuclear 1691 5659 LOC284323 protein, Zinc-finger Contig62628_RC EIF3S9 eukaryotic Hypothetical protein, Initiation factor, 1692 5660 translation initiation Protein biosynthesis, RNA-binding factor 3, subunit 9 eta, 116 kDa Contig62675_RC similar to RIKEN Hypothetical protein 1693 5661 1810056O20 Contig62923_RC FLJ12697 ubiquitin specific Ubl conjugation pathway, Hydrolase, 1694 5662 protease 42 Thiol protease, Multigene family Contig63026 hypothetical protein 1695 5663 LOC285958 Contig63079 FLJ32332 likely ortholog of Hypothetical protein 1696 5664 mouse protein phosphatase 2C eta Contig6323_RC FLJ12581 Nanog homeobox DNA-binding, Homeobox, Nuclear 1697 5665 protein, Hypothetical protein Contig63304 LOC113444 hypothetical protein Hypothetical protein 1698 5666 BC011880 Contig63667_RC MCPR hypothetical protein Ubl conjugation pathway, Cell cycle, 1699 5667 LOC285069 Cell division, Mitosis, Repeat Contig6382_RC Transcribed 1700 5668 sequences Contig63913_RC MGC13016 coiled-coil-helix- 1701 5669 coiled-coil-helix domain containing 6 Contig64214_RC MGC19604 similar to RIKEN Hypothetical protein 1702 5670 cDNA B230118G17 gene Contig64297_RC KIAA1416 KIAA1416 protein Hypothetical protein, Transcription 1703 5671 regulation, Hydrolase, Helicase, Chromatin regulator, Nuclear protein, ATP-binding, DNA-binding, Repeat Contig64390 C20orf92 COMM domain Hypothetical protein 1704 5672 containing 7 Contig64477 Clone 1705 5673 IMAGE: 5742072, mRNA Contig64502 KIAA0303 KIAA0303 protein Hypothetical protein, ATP-binding, 1706 5674 Kinase, Serine/threonine-protein kinase, Transferase Contig64691 UBB ubiquitin B Hypothetical protein 1707 5675 Contig64794 FLJ21156 Homo sapiens Hypothetical protein 1708 5676 cDNA: FLJ21156 fis, clone CAS09878. Contig64940_RC ORAOV1 oral cancer Hypothetical protein 1709 5677 overexpressed 1 Contig65300_RC CDNA FLJ41454 fis, 1710 5678 clone BRSTN2011597 Contig65404 CKLFSF3 chemokine-like Chemotaxis, Cytokine, 1711 5679 factor super family 3 Transmembrane, Alternative splicing Contig65439 C20orf178 chromosome 20 Hypothetical protein 1712 5680 open reading frame 178 Contig65459_RC formin binding Hypothetical protein, SH3 domain 1713 5681 protein 1 Contig65478_RC phosphoglucomutase Hypothetical protein 1714 5682 2-like 1 Contig65900 HMGN3 high mobility group Nuclear protein, DNA-binding, 1715 5683 nucleosomal binding Hypothetical protein domain 3 Contig65934_RC hypothetical gene Hypothetical protein 1716 5684 supported by BC031661 Contig66003_RC MY038 retinoblastoma Hypothetical protein, Metal-binding, 1717 5685 binding protein 6 Zinc, Zinc-finger Contig66028_RC reversion-inducing- Signal, Glycoprotein, GPI-anchor, 1718 5686 cysteine-rich protein Serine protease inhibitor, with kazal motifs Membrane, Anti-oncogene, Repeat, Lipoprotein Contig66129_RC CDNA FLJ13276 fis, 1719 5687 clone OVARC1001040 Contig66573_RC FLJ12567 Clone Hypothetical protein 1720 5688 IMAGE: 5538723, mRNA Contig66615_RC USP9Y Human S6 H-8 Ubiquitin conjugation, Hydrolase, 1721 5689 mRNA expressed in Thiol protease, Multigene family, chromosome 6- Alternative splicing suppressed melanoma cells. Contig66632_RC hypothetical protein 1722 5690 LOC339324 Contig66759_RC MGC16028 MGC16028 similar 1723 5691 to RIKEN cDNA 1700019E19 gene Contig667_RC ADAM17 hypothetical protein Hydrolase, Metalloprotease, Zinc, 1724 5692 LOC285148 Signal, Glycoprotein, Zymogen, Transmembrane, SH3-binding, Phosphorylation, Alternative splicing, 3D-structure Contig66868_RC ze63e05.s1 Soares 1725 5693 retina N2b4HR Homo sapiens cDNA clone IMAGE: 363680 3′, mRNA sequence. Contig66904_RC MGC4368 hypothetical protein Hypothetical protein 1726 5694 MGC4368 Contig684_RC RPS3A ring finger protein 12 Transcription regulation, Zinc-finger, 1727 5695 Hypothetical protein, Metal-binding Contig693_RC NFIA nuclear factor I/A Activator, DNA replication, DNA- 1728 5696 binding, Nuclear protein, Transcription, Transcription regulation, Multigene family Contig706_RC CDNA FLJ32401 fis, 1729 5697 clone SKMUS2000339 Contig726_RC FLJ13725 hypothetical protein Hypothetical protein 1730 5698 FLJ13725 Contig732_RC FTH1 transducer of Hypothetical protein 1731 5699 regulated cAMP response element- binding protein (CREB) 2 Contig7401_RC FLJ22756 PDZ domain Hypothetical protein 1732 5700 containing 2 Contig75_RC RPS6KA2 ribosomal protein S6 ATP-binding, Kinase, 1733 5701 kinase, 90 kDa, Serine/threonine-protein kinase, polypeptide 2 Transferase, Repeat, Multigene family, Phosphorylation, Nuclear protein Contig773 FLJ20989 hypothetical protein Hypothetical protein 1734 5702 FLJ20989 Contig8210_RC DJ467N11.1 dJ467N11.1 protein ATP-binding, Helicase, Hydrolase, 1735 5703 Hypothetical protein Contig830_RC C1orf13 N-acetylneuraminate 1736 5704 pyruvate lyase (dihydrodipicolinate synthase) Contig8371_RC Transcribed 1737 5705 sequences Contig842_RC human T-cell Transcription regulation, DNA- 1738 5706 leukemia virus binding, Nuclear protein enhancer factor Contig844_RC DKFZP566M1046 hypothetical protein Hypothetical protein 1739 5707 DKFZp566M1046 Contig8547_RC Transcribed 1740 5708 sequences Contig883_RC KIAA1813 KIAA1813 protein Hypothetical protein 1741 5709 Contig8885_RC HCS cytochrome c, Mitochondrion, Electron transport, 1742 5710 somatic Respiratory chain, Heme, Acetylation, Polymorphism, Apoptosis Contig8909_RC MGC45404 TAK1-binding Hypothetical protein 1743 5711 protein 3 Contig8956_RC FLJ13158 chromosome 6 open Hypothetical protein 1744 5712 reading frame 134 Contig8963_RC wi72b03.x1 1745 5713 NCI_CGAP_Kid12 Homo sapiens cDNA clone IMAGE: 2398829 3′, mRNA sequence. Contig8980_RC DKFZP564B1162 hypothetical protein Hypothetical protein 1746 5714 DKFZp564B1162 Contig9042_RC Transcribed 1747 5715 sequences Contig9059_RC FLJ12118 hypothetical protein Hypothetical protein 1748 5716 FLJ12118 Contig9136_RC CDNA FLJ43053 fis, 1749 5717 clone BRTHA3006856 Contig9380_RC Transcribed 1750 5718 sequences Contig9514_RC Transcribed 1751 5719 sequences Contig9518_RC ZNF287 zinc finger protein Metal-binding, Zinc, Zinc-finger, 1752 5720 287 Transcription regulation, Nuclear protein, DNA-binding, Repeat Contig964_RC MGC10433 hypothetical protein Hypothetical protein 1753 5721 MGC10433 Contig9714_RC MRNA for Hypothetical protein 1754 5722 hypothetical protein (ORF1), clone 00275 Contig973_RC MRPL45 mitochondrial Ribosomal protein, Mitochondrion, 1755 5723 ribosomal protein Transit peptide L45 Contig9810_RC KCNE1 potassium voltage- Transport, Ion transport, Ionic 1756 5724 gated channel, lsk- channel, Voltage-gated channel, related family, Potassium channel, Potassium, member 1 Potassium transport, Transmembrane, Phosphorylation, Glycoprotein, Polymorphism, Disease mutation, Long QT syndrome, Deafness Contig9965_RC DHODH dihydroorotate Pyrimidine biosynthesis, 1757 5725 dehydrogenase Oxidoreductase, Flavoprotein, FAD, Transit peptide, Mitochondrion, 3D- structure D10040 FACL2 acyl-CoA synthetase Ligase, Fatty acid metabolism, 1758 5726 long-chain family Magnesium, Multigene family, member 1 Hypothetical protein D13642 SF3B3 splicing factor 3b, Spliceosome, mRNA processing, 1759 5727 subunit 3, 130 kDa mRNA splicing, Nuclear protein, Hypothetical protein D16816 REG1B regenerating islet- Glycoprotein, Signal, Lectin, 1760 5728 derived 1 beta Pyrrolidone carboxylic acid (pancreatic stone protein, pancreatic thread protein) D21064 INPP5E peptidase Hypothetical protein, Hydrolase, 1761 5729 (mitochondrial Metalloprotease, Mitochondrion, processing) alpha Transit peptide D25218 RRS1 RRS1 ribosome Ribosome biogenesis, Nuclear 1762 5730 biogenesis regulator protein homolog (S. cerevisiae) D25328 PFKP phosphofructokinase, Kinase, Transferase, Glycolysis, 1763 5731 platelet Repeat, Allosteric enzyme, Phosphorylation, Magnesium, Multigene family D26070 ITPR1 inositol 1,4,5- Receptor, Transmembrane, 1764 5732 triphosphate Phosphorylation, Endoplasmic receptor, type 1 reticulum, Ionic channel, Ion transport, Calcium channel, Alternative splicing, Repeat D26362 BRD3 bromodomain Bromodomain, Repeat, Nuclear 1765 5733 containing 3 protein D26488 KIAA0007 KIAA0007 protein Hypothetical protein, Repeat, WD 1766 5734 repeat D29954 KIAA0056 KIAA0056 protein Hypothetical protein 1767 5735 D29958 KIAA0116 KIAA0116 protein Exosome, Hydrolase, Nuclease, 1768 5736 Exonuclease, rRNA processing, Nuclear protein, RNA-binding, Polymorphism, Hypothetical protein D31886 RAB3GAP RAB3 GTPase- Hypothetical protein 1769 5737 ACTIVATING PROTEIN D31887 KIAA0062 solute carrier family Hypothetical protein 1770 5738 39 (zinc transporter), member 14 D38435 PMS2L1 postmeiotic Hypothetical protein, DNA repair, 1771 5739 segregation Anti-oncogene, Nuclear protein, increased 2-like 6 Polymorphism, Disease mutation, Hereditary nonpolyposis colorectal cancer, 3D-structure D38522 SYT11 Homo sapiens Transmembrane, Repeat, Synapse, 1772 5740 KIAA0080 mRNA, Hypothetical protein partial cds. D38549 CYFIP1 cytoplasmic FMR1 Hypothetical protein 1773 5741 interacting protein 1 D42043 KIAA0084 raft-linking protein Hypothetical protein 1774 5742 D42084 METAP1 methionyl Hydrolase, Aminopeptidase, Cobalt 1775 5743 aminopeptidase 1 D43948 KIAA0097 KIAA0097 gene Hypothetical protein, Repeat 1776 5744 product D43949 KIAA0082 KIAA0082 Hypothetical protein 1777 5745 D50402 SLC11A1 solute carrier family Transport, Iron transport, 1778 5746 11 (proton-coupled Transmembrane, Glycoprotein, divalent metal ion Macrophage, Polymorphism transporters), member 1 D50911 GSA7 KIAA0121 gene Hypothetical protein 1779 5747 product D50918 6-Sep septin 6 Cell division, GTP-binding, Coiled 1780 5748 coil, Alternative splicing D63487 KIAA0153 KIAA0153 protein Hypothetical protein 1781 5749 D79998 KCTD2 potassium channel Hypothetical protein 1782 5750 tetramerisation domain containing 2 D80007 PDCD11 programmed cell Nuclear protein, rRNA processing, 1783 5751 death 11 Repeat, Polymorphism D80010 LPIN1 lipin 1 Nuclear protein, Polymorphism 1784 5752 D83781 NUP160 nucleoporin 160 kDa Nuclear protein, Transport, 1785 5753 Alternative splicing, Hypothetical protein D84294 TTC3 tetratricopeptide Repeat, TPR repeat, Zinc-finger, 1786 5754 repeat domain 3 Alternative splicing, Polymorphism, Metal-binding D86964 DOCK2 dedicator of Guanine-nucleotide releasing factor, 1787 5755 cytokinesis 2 Membrane, Cytoskeleton, SH3 domain, Alternative splicing, Polymorphism D86973 GCN1L1 GCN1 general Hypothetical protein 1788 5756 control of amino-acid synthesis 1-like 1 (yeast) D86976 HA-1 minor 1789 5757 histocompatibility antigen HA-1 D87442 NCSTN nicastrin Transmembrane, Glycoprotein, 1790 5758 Signal, Alternative splicing D87449 SLC35D1 solute carrier family Transport, Sugar transport, 1791 5759 35 (UDP-glucuronic Transmembrane, Endoplasmic acid/UDP-N- reticulum acetylgalactosamine dual transporter), member D1 D87453 MRPS27 mitochondrial Hypothetical protein, Ribosomal 1792 5760 ribosomal protein protein, Mitochondrion S27 D87466 KIAA0276 KIAA0276 protein Hypothetical protein 1793 5761 G26403 C9orf19 chromosome 9 open Hypothetical protein 1794 5762 reading frame 19 J03077 PSAP prosaposin (variant Signal, Glycoprotein, Lysosome, 1795 5763 Gaucher disease Sphingolipid metabolism, Repeat, and variant Gaucher disease, GM2- metachromatic gangliosidosis, Disease mutation, leukodystrophy) Metachromatic leukodystrophy, Alternative splicing, 3D-structure J03796 EPB41 erythrocyte Structural protein, Alternative 1796 5764 membrane protein splicing, Cytoskeleton, Actin-binding, band 4.1 Phosphorylation, Pyropoikilocytosis, (elliptocytosis 1, RH- Glycoprotein, Elliptocytosis, linked) Hereditary hemolytic anemia, Polymorphism, 3D-structure J04162 FCGR3A Fc fragment of IgG, Receptor, IgG-binding protein, 1797 5765 low affinity IIIa, Transmembrane, Glycoprotein, receptor for (CD16) Signal, Immunoglobulin domain, Repeat, Multigene family, Polymorphism, GPI-anchor, 3D- structure, Lipoprotein J04178 HEXA hexosaminidase A Hydrolase, Glycosidase, Lysosome, 1798 5766 (alpha polypeptide) GM2-gangliosidosis, Signal, Zymogen, Glycoprotein, Disease mutation, Polymorphism, 3D- structure K02276 MYC v-myc Proto-oncogene, Nuclear protein, 1799 5767 myelocytomatosis DNA-binding, Phosphorylation, viral oncogene Transcription regulation, Activator, homolog (avian) Glycoprotein, Polymorphism, 3D- structure. K02403 C4A complement Complement pathway, Plasma, 1800 5768 component 4A Glycoprotein, Sulfation, Signal, Inflammatory response, Polymorphism, Disease mutation, Blood group antigen, Thioester bond L00635 FNTB farnesyltransferase, Plasmid, Transferase, 1801 5769 CAAX box, beta Prenyltransferase, Repeat, Zinc L08246 MCL1 myeloid cell Apoptosis, Transmembrane, 1802 5770 leukemia sequence Differentiation, Alternative splicing 1 (BCL2-related) L20688 ARHGDIB Rho GDP GTPase activation, 3D-structure 1803 5771 dissociation inhibitor (GDI) beta L21961 IGL@ Human Ig Immunoglobulin domain, 1804 5772 rearranged lambda- Hypothetical protein, chain mRNA, Immunoglobulin C region, 3D- subgroup VL3, V-J structure region, partial cds. L22005 CDC34 cell division cycle 34 Ubl conjugation pathway, Ligase, 1805 5773 Multigene family, Hypothetical protein, Cell division L27943 CDA cytidine deaminase Hydrolase, Zinc 1806 5774 L35035 RPIA ribose 5-phosphate Isomerase 1807 5775 isomerase A (ribose 5-phosphate epimerase) L39061 TAF1B TATA box binding Hypothetical protein 1808 5776 protein (TBP)- associated factor, RNA polymerase I, B, 63 kDa L40027 GSK3A glycogen synthase Transferase, Serine/threonine- 1809 5777 kinase 3 alpha protein kinase, ATP-binding, Multigene family, Phosphorylation M12679 HLA-C major Glycoprotein, Signal, 1810 5778 histocompatibility Transmembrane, Hypothetical complex, class I, C protein, MHC, MHC I, Polymorphism, 3D-structure, Alternative splicing M12758 HLA-C Human MHC class I Glycoprotein, Transmembrane 1811 5779 HLA-A cell surface antigen mRNA, (HLA-A2, -B7, -C), clone JY103. M17733 TMSB4X thymosin, beta 4, X- Actin-binding, Cytoskeleton, 1812 5780 linked Acetylation M26383 IL8 interleukin 8 Cytokine, Chemotaxis, Inflammatory 1813 5781 response, Signal, Alternative splicing, 3D-structure M31212 MYL6 myosin, light Myosin, Muscle protein, Acetylation, 1814 5782 polypeptide 6, alkali, Alternative splicing, Multigene family smooth muscle and non-muscle M31523 TCF3 transcription factor 3 Transcription regulation, DNA- 1815 5783 (E2A binding, Nuclear protein, Proto- immunoglobulin oncogene, Chromosomal enhancer binding translocation, Alternative splicing, factors E12/E47) Phosphorylation, 3D-structure M33552 LSP1 lymphocyte-specific T-cell, Phosphorylation, 1816 5784 protein 1 Polymorphism M34671 CD59 CD59 antigen p18-20 Antigen, Glycoprotein, GPI-anchor, 1817 5785 (antigen identified Signal, 3D-structure, Lipoprotein by monoclonal antibodies 16.3A5, EJ16, EJ30, EL32 and G344) M37712 CDC2L2 Homo sapiens Apoptosis, Transferase, 1818 5786 p58/GTA protein Serine/threonine-protein kinase, kinase mRNA, ATP-binding, Cell cycle, complete cds. Phosphorylation, Alternative splicing, Alternative initiation M60721 HLX1 H2.0-like homeo box DNA-binding, Homeobox, Nuclear 1819 5787 1 (Drosophila) protein, Transcription regulation M63438 IGKC Immunoglobulin Hypothetical protein 1820 5788 kappa light chain mRNA, partial cds M65292 HFL1 H factor Repeat, Glycoprotein, Sushi, Signal, 1821 5789 (complement)-like 1 Polymorphism M74782 IL3RA interleukin 3 Receptor, Transmembrane, 1822 5790 receptor, alpha (low Glycoprotein, Signal affinity) M83822 LRBA LPS-responsive Repeat, WD repeat 1823 5791 vesicle trafficking, beach and anchor containing M90657 TM4SF1 Human tumor Glycoprotein, Antigen, 1824 5792 antigen (L6) mRNA, Transmembrane complete cds. M91211 AGER advanced Immunoglobulin domain, 1825 5793 glycosylation end Glycoprotein, Transmembrane, product-specific Repeat, Signal, Alternative splicing, receptor Polymorphism, Receptor M92439 LRPPRC leucine-rich PPR- Hypothetical protein, Repeat 1826 5794 motif containing M92642 COL16A1 collagen, type XVI, Extracellular matrix, Connective 1827 5795 alpha 1 tissue, Collagen, Hydroxylation, Repeat, Signal M94362 LMNB2 Human lamin B2 Intermediate filament, Coiled coil, 1828 5796 (LAMB2) mRNA, Nuclear protein, Lipoprotein, partial cds. Prenylation, Phosphorylation, Hypothetical protein NM_000016 ACADM acyl-Coenzyme A Oxidoreductase, Flavoprotein, FAD, 1829 5797 dehydrogenase, C-4 Fatty acid metabolism, to C-12 straight Mitochondrion, Transit peptide, chain Disease mutation, 3D-structure NM_000018 ACADVL acyl-Coenzyme A Oxidoreductase, Flavoprotein, FAD, 1830 5798 dehydrogenase, very Fatty acid metabolism, long chain Mitochondrion, Transit peptide, Alternative splicing, Disease mutation, Polymorphism, Cardiomyopathy NM_000021 PSEN1 presenilin 1 Transmembrane, Phosphorylation, 1831 5799 (Alzheimer disease Endoplasmic reticulum, Golgi stack, 3) Alzheimer's disease, Disease mutation, Polymorphism, Alternative splicing NM_000022 ADA adenosine Hydrolase, Nucleotide metabolism, 1832 5800 deaminase SCID, Hereditary hemolytic anemia, Disease mutation, Polymorphism NM_000026 ADSL adenylosuccinate Purine biosynthesis, Lyase, 1833 5801 lyase Alternative splicing, Disease mutation, Epilepsy NM_000030 AGXT alanine-glyoxylate Aminotransferase, Transferase, 1834 5802 aminotransferase Pyridoxal phosphate, Peroxisome, (oxalosis I; Mitochondrion, Disease mutation, hyperoxaluria I; Polymorphism glycolicaciduria; serine-pyruvate aminotransferase) NM_000034 ALDOA aldolase A, fructose- Lyase, Schiff base, Glycolysis, 1835 5803 bisphosphate Multigene family, 3D-structure, Disease mutation NM_000045 ARG1 arginase, liver Urea cycle, Arginine metabolism, 1836 5804 Hydrolase, Manganese, Disease mutation, Polymorphism NM_000056 BCKDHB branched chain keto Oxidoreductase, Mitochondrion, 1837 5805 acid dehydrogenase Transit peptide, Disease mutation, E1, beta polypeptide Maple syrup urine disease, 3D- (maple syrup urine structure disease) NM_000070 CAPN3 calpain 3, (p94) Hydrolase, Thiol protease, Calcium- 1838 5806 binding, Multigene family, Repeat, Disease mutation, Polymorphism, Alternative splicing NM_000073 CD3G CD3G antigen, Immunoglobulin domain, T-cell, 1839 5807 gamma polypeptide Receptor, Transmembrane, (TiT3 complex) Glycoprotein, Signal NM_000074 TNFSF5 tumor necrosis factor Cytokine, Transmembrane, 1840 5808 (ligand) superfamily, Glycoprotein, Signal-anchor, member 5 (hyper- Antigen, Disease mutation, IgM syndrome) Polymorphism, 3D-structure NM_000081 CHS1 Chediak-Higashi Protein transport, Transport, Repeat, 1841 5809 syndrome 1 WD repeat, Disease mutation, Alternative splicing NM_000082 CKN1 Cockayne syndrome Nuclear protein, Repeat, WD repeat, 1842 5810 1 (classical) Transcription regulation, Polymorphism, Cockayne's syndrome, Deafness, Dwarfism NM_000095 COMP cartilage oligomeric Hypothetical protein, Glycoprotein, 1843 5811 matrix protein Cell adhesion, Calcium-binding, (pseudoachondroplasia, Repeat, EGE-like domain, Signal, epiphyseal Disease mutation, Polymorphism dysplasia 1, multiple) NM_000099 CST3 cystatin C (amyloid Thiol protease inhibitor, Amyloid, 1844 5812 angiopathy and Signal, Disease mutation, cerebral Polymorphism, 3D-structure hemorrhage) NM_000100 CSTB cystatin B (stefin B) Thiol protease inhibitor, Nuclear 1845 5813 protein, Acetylation, Disease mutation, Epilepsy, 3D-structure NM_000101 CYBA cytochrome b-245, Oxidoreductase, NADP, Electron 1846 5814 alpha polypeptide transport, Membrane, Heme, Polymorphism, Disease mutation, Chronic granulomatous disease, Hypothetical protein NM_000116 TAZ tafazzin Alternative splicing, 1847 5815 (cardiomyopathy, Transmembrane, Disease mutation dilated 3A (X-linked); endocardial fibroelastosis 2; Barth syndrome) NM_000120 EPHX1 epoxide hydrolase 1, Hydrolase, Endoplasmic reticulum, 1848 5816 microsomal Detoxification, Transmembrane, (xenobiotic) Aromatic hydrocarbons catabolism, Microsome, Polymorphism NM_000121 EPOR erythropoietin Receptor, Transmembrane, 1849 5817 receptor Glycoprotein, Signal, Phosphorylation, 3D-structure NM_000126 ETFA electron-transfer- Electron transport, Flavoprotein, 1850 5818 flavoprotein, alpha FAD, Mitochondrion, Transit peptide, polypeptide (glutaric Disease mutation, Glutaricaciduria, aciduria II) Polymorphism, 3D-structure NM_000130 F5 coagulation factor V Blood coagulation, Glycoprotein, 1851 5819 (proaccelerin, labile Sulfation, Calcium, Signal, Zymogen, factor) Repeat, Polymorphism, Disease mutation, Thrombophilia, 3D- structure NM_000143 FH fumarate hydratase Lyase, Tricarboxylic acid cycle, 1852 5820 Mitochondrion, Transit peptide, Acetylation, Alternative initiation, Anti-oncogene, Disease mutation NM_000146 FTL ferritin, light Hypothetical protein, Iron storage, 1853 5821 polypeptide Metal-binding, Acetylation NM_000151 G6PC glucose-6- Glycogen biosynthesis, Hydrolase, 1854 5822 phosphatase, Transmembrane, Glycoprotein, catalytic (glycogen Endoplasmic reticulum, Glycogen storage disease type storage disease, Disease mutation, I, von Gierke Polymorphism disease) NM_000156 GAMT guanidinoacetate N- Transferase, Methyltransferase 1855 5823 methyltransferase NM_000157 GBA glucosidase, beta; Glycosidase, Hydrolase, Signal, 1856 5824 acid (includes Hypothetical protein, Sphingolipid glucosylceramidase) metabolism, Glycoprotein, Lysosome, Membrane, Gaucher disease, Disease mutation, Polymorphism, Alternative initiation, Pharmaceutical NM_000175 GPI glucose phosphate Gluconeogenesis, Glycolysis, 1857 5825 isomerase Isomerase, Growth factor, Cytokine, Disease mutation, 3D-structure, Hypothetical protein NM_000177 GSN gelsolin Cytoskeleton, Actin-binding, Repeat, 1858 5826 (amyloidosis, Finnish Calcium, Alternative initiation, type) Signal, Amyloid, Disease mutation, 3D-structure, Phosphorylation, Actin capping NM_000181 GUSB glucuronidase, beta Hydrolase, Glycosidase, Lysosome, 1859 5827 Glycoprotein, Signal, Mucopolysaccharidosis, Disease mutation, 3D-structure, Alternative splicing, Polymorphism NM_000183 HADHB hydroxyacyl- Fatty acid metabolism, Transferase, 1860 5828 Coenzyme A Acyltransferase, Mitochondrion, dehydrogenase/3- Transit peptide, Disease mutation, ketoacyl-Coenzyme Hypothetical protein A thiolase/enoyl- Coenzyme A hydratase (trifunctional protein), beta subunit NM_000186 HF1 H factor 1 Complement alternate pathway, 1861 5829 (complement) Plasma, Glycoprotein, Repeat, Sushi, Signal, 3D-structure, Polymorphism, Alternative splicing NM_000206 IL2RG interleukin 2 Receptor, Transmembrane, 1862 5830 receptor, gamma Glycoprotein, Signal, Disease (severe combined mutation, SCID, 3D-structure immunodeficiency) NM_000211 ITGB2 integrin, beta 2 Integrin, Cell adhesion, Receptor, 1863 5831 (antigen CD18 (p95), Transmembrane, Glycoprotein, lymphocyte function- Repeat, Signal, Disease mutation, associated antigen Pyrrolidone carboxylic acid, 3D- 1; macrophage structure antigen 1 (mac-1) beta subunit) NM_000229 LCAT lecithin-cholesterol Cholesterol metabolism, Lipid 1864 5832 acyltransferase metabolism, Transferase, Acyltransferase, Signal, Glycoprotein, Polymorphism, Disease mutation NM_000235 LIPA lipase A, lysosomal Hydrolase, Lipid degradation, 1865 5833 acid, cholesterol Glycoprotein, Signal, Lysosome, esterase (Wolman Disease mutation, Polymorphism disease) NM_000239 LYZ lysozyme (renal Hydrolase, Glycosidase, 1866 5834 amyloidosis) Bacteriolytic enzyme, Signal, Amyloid, 3D-structure, Disease mutation, Polymorphism NM_000243 MEFV Mediterranean fever Inflammatory response, Actin- 1867 5835 binding, Metal-binding, Cytoskeleton, Microtubule, Nuclear protein, Zinc- finger, Zinc, Polymorphism, Disease mutation, Alternative splicing NM_000249 MLH1 mutL homolog 1, DNA repair, Nuclear protein, 1868 5836 colon cancer, Disease mutation, Anti-oncogene, nonpolyposis type 2 Polymorphism, Hereditary (E. coli) nonpolyposis colorectal cancer NM_000250 MPO myeloperoxidase Oxidoreductase, Peroxidase, Iron, 1869 5837 Heme, Calcium-binding, Glycoprotein, Signal, Oxidation, Lysosome, Alternative splicing, Polymorphism, Disease mutation, 3D-structure NM_000254 MTR 5- Transferase, Methyltransferase, 1870 5838 methyltetrahydrofolate- Methionine biosynthesis, Vitamin homocysteine B12, Cobalt, Disease mutation, methyltransferase Polymorphism NM_000265 NCF1 neutrophil cytosolic SH3 domain, Repeat, 1871 5839 factor 1 (47 kDa, Polymorphism, Disease mutation, chronic Chronic granulomatous disease, 3D- granulomatous structure disease, autosomal 1) NM_000269 NME1 non-metastatic cells Transferase, Kinase, ATP-binding, 1872 5840 1, protein (NM23A) Nuclear protein, Anti-oncogene, expressed in Disease mutation, 3D-structure NM_000270 NP nucleoside Hypothetical protein, Transferase, 1873 5841 phosphorylase Glycosyltransferase, Polymorphism, Disease mutation, 3D-structure NM_000285 PEPD peptidase D Collagen degradation, Hydrolase, 1874 5842 Dipeptidase, Metalloprotease, Manganese, Acetylation, Polymorphism, Disease mutation NM_000288 PEX7 peroxisomal Repeat, WD repeat, Peroxisome, 1875 5843 biogenesis factor 7 Transport, Protein transport, Rhizomelic chondrodysplasia punctata, Disease mutation, Polymorphism NM_000289 PFKM phosphofructokinase, Glycolysis, Kinase, Transferase, 1876 5844 muscle Repeat, Allosteric enzyme, Phosphorylation, Magnesium, Multigene family, Alternative splicing, Disease mutation, Glycogen storage disease NM_000291 PGK1 phosphoglycerate Transferase, Kinase, Multigene 1877 5845 kinase 1 family, Glycolysis, Acetylation, Disease mutation, Polymorphism, Hereditary hemolytic anemia NM_000295 SERPINA1 serine (or cysteine) Serpin, Serine protease inhibitor, 1878 5846 proteinase inhibitor, Glycoprotein, Plasma, clade A (alpha-1 Polymorphism, Acute phase, Signal, antiproteinase, 3D-structure, Disease mutation, antitrypsin), member 1 Protease inhibitor NM_000297 PKD2 polycystic kidney Ionic channel, Glycoprotein, Coiled 1879 5847 disease 2 coil, Transmembrane, Calcium- (autosomal binding, Disease mutation, dominant) Polymorphism NM_000302 PLOD procollagen-lysine, Oxidoreductase, Dioxygenase, 1880 5848 2-oxoglutarate 5- Signal, Iron, Vitamin C, Glycoprotein, dioxygenase (lysine Endoplasmic reticulum, Membrane, hydroxylase, Ehlers- Polymorphism, Disease mutation, Danlos syndrome Ehlers-Danlos syndrome type VI) NM_000305 PON2 paraoxonase 2 Hydrolase, Glycoprotein, Signal, 1881 5849 Membrane, Multigene family, Polymorphism, Alternative splicing NM_000307 POU3F4 POU domain, class Transcription regulation, Nuclear 1882 5850 3, transcription factor 4 protein, DNA-binding, Homeobox, Disease mutation, Deafness NM_000320 QDPR quinoid Tetrahydrobiopterin biosynthesis, 1883 5851 dihydropteridine Oxidoreductase, NADP, 3D- reductase structure, Polymorphism, Phenylketonuria, Disease mutation NM_000321 RB1 retinoblastoma 1 Transcription regulation, DNA- 1884 5852 (including binding, Nuclear protein, osteosarcoma) Phosphorylation, Anti-oncogene, Disease mutation, 3D-structure NM_000327 ROM1 retinal outer Vision, Cell adhesion, 1885 5853 segment membrane Photoreceptor, Transmembrane, protein 1 Polymorphism, Disease mutation, Retinitis pigmentosa NM_000376 VDR vitamin D (1,25- Receptor, Transcription regulation, 1886 5854 dihydroxyvitamin D3) DNA-binding, Nuclear protein, Zinc- receptor finger, Phosphorylation, Disease mutation, 3D-structure NM_000377 WAS Wiskott-Aldrich Repeat, Disease mutation, 1887 5855 syndrome (eczema- Phosphorylation, 3D-structure thrombocytopenia) NM_000380 XPA xeroderma DNA repair, DNA-binding, Zinc- 1888 5856 pigmentosum, finger, Nuclear protein, Xeroderma complementation pigmentosum, Disease mutation, group A Polymorphism, 3D-structure NM_000386 BLMH bleomycin hydrolase Hydrolase, Thiol protease, 1889 5857 Polymorphism, 3D-structure, Hypothetical protein NM_000392 ABCC2 ATP-binding ATP-binding, Glycoprotein, 1890 5858 cassette, sub-family Transmembrane, Transport, Repeat, C (CFTR/MRP), Disease mutation, Polymorphism member 2 NM_000394 CRYAA crystallin, alpha A Eye lens protein, Acetylation, 1891 5859 Glycoprotein, Disease mutation, Vision NM_000397 CYBB cytochrome b-245, Oxidoreductase, NADP, Electron 1892 5860 beta polypeptide transport, Transmembrane, FAD, (chronic Heme, Glycoprotein, Voltage-gated granulomatous channel, Ionic channel, Disease disease) mutation, Chronic granulomatous disease NM_000399 EGR2 early growth Transcription regulation, Activator, 1893 5861 response 2 (Krox-20 DNA-binding, Nuclear protein, homolog, Repeat, Zinc-finger, Metal-binding, Drosophila) Alternative splicing, Disease mutation, Charcot-Marie-Tooth disease, Dejerine-Sottas syndrome NM_000401 EXT2 exostoses (multiple) 2 Transferase, Glycosyltransferase, 1894 5862 Endoplasmic reticulum, Golgi stack, Transmembrane, Signal-anchor, Glycoprotein, Anti-oncogene, Disease mutation, Hereditary multiple exostoses, Alternative splicing NM_000402 G6PD glucose-6-phosphate Oxidoreductase, NADP, Glucose 1895 5863 dehydrogenase metabolism, Disease mutation, Polymorphism, Hereditary hemolytic anemia, Alternative splicing, Acetylation NM_000404 GLB1 galactosidase, beta 1 Hydrolase, Glycosidase, Lysosome, 1896 5864 Signal, Alternative splicing, Glycoprotein, Polymorphism, Disease mutation NM_000405 GM2A GM2 ganglioside Signal, Glycoprotein, Lysosome, 1897 5865 activator protein Sphingolipid metabolism, GM2- gangliosidosis, Disease mutation, Polymorphism, 3D-structure NM_000407 GP1BB glycoprotein lb Hypothetical protein, Cell division, 1898 5866 (platelet), beta GTP-binding, Coiled coil, Platelet, polypeptide Transmembrane, Glycoprotein, Hemostasis, Blood coagulation, Signal, Phosphorylation, Cell adhesion, Leucine-rich repeat NM_000418 IL4R interleukin 4 receptor Receptor, Transmembrane, 1899 5867 Glycoprotein, Signal, Disease mutation, Polymorphism, 3D- structure NM_000425 L1CAM L1 cell adhesion Neurogenesis, Cell adhesion, 1900 5868 molecule Developmental protein, (hydrocephalus, Glycoprotein, Transmembrane, stenosis of aqueduct Repeat, Antigen, Immunoglobulin of Sylvius 1, MASA domain, Signal, Disease mutation, (mental retardation, Alternative splicing aphasia, shuffling gait and adducted thumbs) syndrome, spastic paraplegia 1) NM_000433 NCF2 neutrophil cytosolic SH3 domain, Repeat, TPR repeat, 1901 5869 factor 2 (65 kDa, Chronic granulomatous disease, chronic Disease mutation, 3D-structure granulomatous disease, autosomal 2) NM_000434 NEU1 sialidase 1 Hydrolase, Glycosidase, Signal, 1902 5870 (lysosomal sialidase) Repeat, Glycoprotein, Disease mutation, Polymorphism, Phosphorylation NM_000436 OXCT 3-oxoacid CoA Mitochondrion, Transferase, Transit 1903 5871 transferase peptide, Disease mutation, Polymorphism NM_000445 PLEC1 plectin 1, Coiled coil, Repeat, Structural 1904 5872 intermediate filament protein, Cytoskeleton, Actin-binding, binding protein Phosphorylation, Alternative splicing, 500 kDa Epidermolysis bullosa, Disease mutation NM_000454 SOD1 superoxide Antioxidant, Oxidoreductase, Metal- 1905 5873 dismutase 1, soluble binding, Copper, Zinc, Acetylation, (amyotrophic lateral 3D-structure, Amyotrophic lateral sclerosis 1 (adult)) sclerosis, Disease mutation NM_000456 SUOX sulfite oxidase Oxidoreductase, Mitochondrion, 1906 5874 Heme, Molybdenum, Transit peptide, Disease mutation, 3D-structure NM_000462 UBE3A ubiquitin protein Ligase, Nuclear protein, Ubl 1907 5875 ligase E3A (human conjugation pathway, Alternative papilloma virus E6- splicing, Disease mutation, associated protein, Polymorphism, 3D-structure, Angelman Hypothetical protein syndrome) NM_000476 AK1 adenylate kinase 1 Transferase, Kinase, ATP-binding, 1908 5876 Acetylation, Disease mutation NM_000480 AMPD3 adenosine Hydrolase, Nucleotide metabolism, 1909 5877 monophosphate Multigene family, Polymorphism, deaminase (isoform Alternative splicing E) NM_000481 AMT aminomethyltransferase Hypothetical protein, Transferase, 1910 5878 (glycine Aminotransferase, Mitochondrion, cleavage system Transit peptide, Disease mutation protein T) NM_000487 ARSA arylsulfatase A Hydrolase, Signal, Glycoprotein, 1911 5879 Lysosome, Disease mutation, Metachromatic leukodystrophy, Sphingolipid metabolism, Polymorphism, 3D-structure NM_000497 CYP11B1 cytochrome P450, Steroidogenesis, Electron transport, 1912 5880 family 11, subfamily Steroid metabolism, Oxidoreductase, B, polypeptide 1 Monooxygenase, Mitochondrion, Membrane, Heme, Transit peptide, Polymorphism, Disease mutation NM_000502 EPX eosinophil Oxidoreductase, Peroxidase, Iron, 1913 5881 peroxidase Heme, Glycoprotein, Signal, Disease mutation NM_000507 FBP1 fructose-1,6- Hydrolase, Carbohydrate 1914 5882 bisphosphatase 1 metabolism, Gluconeogenesis, Zinc, Allosteric enzyme, Disease mutation, Polymorphism, 3D-structure, Hypothetical protein NM_000512 GALNS galactosamine (N- Hypothetical protein 1915 5883 acetyl)-6-sulfate sulfatase (Morquio syndrome, mucopolysaccharidosis type IVA) NM_000517 HBA2 hemoglobin, alpha 2 Heme, Oxygen transport, Transport, 1916 5884 Erythrocyte, Disease mutation, Polymorphism, Acetylation, 3D- structure NM_000525 KCNJ11 potassium inwardly- Ionic channel, Ion transport, Voltage- 1917 5885 rectifying channel, gated channel, Transmembrane, subfamily J, member Potassium transport, Polymorphism, 11 Disease mutation, Diabetes mellitus NM_000528 MAN2B1 mannosidase, alpha, Glycosidase, Hydrolase, 1918 5886 class 2B, member 1 Glycoprotein, Lysosome, Zymogen, Signal, Disease mutation, Polymorphism NM_000532 PCCB propionyl Coenzyme Hypothetical protein, Mitochondrion, 1919 5887 A carboxylase, beta Transit peptide, Ligase, Disease polypeptide mutation NM_000542 SFTPB surfactant, Surface film, Gaseous exchange, 1920 5888 pulmonary- Glycoprotein, Repeat, associated protein B Polymorphism, 3D-structure NM_000558 HBA1 hemoglobin, alpha 2 Heme, Oxygen transport, Transport, 1921 5889 Erythrocyte, Disease mutation, Polymorphism, Acetylation, 3D- structure NM_000565 IL6R interleukin 6 receptor Receptor, Transmembrane, 1922 5890 Glycoprotein, Immunoglobulin domain, Repeat, Alternative splicing, Signal, 3D-structure NM_000569 FCGR3A Fc fragment of IgG, IgG-binding protein, Receptor, 1923 5891 low affinity IIIa, Transmembrane, Glycoprotein, receptor for (CD16) Signal, Immunoglobulin domain, Repeat, Multigene family, Polymorphism, GPI-anchor, 3D- structure, Lipoprotein NM_000573 CR1 complement Complement pathway, Glycoprotein, 1924 5892 component (3b/4b) Transmembrane, Repeat, Signal, receptor 1, including Receptor, Sushi, Blood group Knops blood group antigen, Polymorphism, Pyrrolidone system carboxylic acid, 3D-structure NM_000578 SLC11A1 solute carrier family Transport, Iron transport, 1925 5893 11 (proton-coupled Transmembrane, Glycoprotein, divalent metal ion Macrophage, Polymorphism transporters), member 1 NM_000581 GPX1 glutathione Oxidoreductase, Peroxidase, 1926 5894 peroxidase 1 Selenium, Selenocysteine, Erythrocyte, Polymorphism, Hypothetical protein NM_000584 IL8 interleukin 8 Cytokine, Chemotaxis, Inflammatory 1927 5895 response, Signal, Alternative splicing, 3D-structure NM_000591 CD14 CD14 antigen Immune response, Inflammatory 1928 5896 response, Signal, GPI-anchor, Repeat, Leucine-rich repeat, Glycoprotein, Antigen, Lipoprotein NM_000607 ORM1 orosomucoid 1 Glycoprotein, Plasma, Acute phase, 1929 5897 Signal, Lipocalin, Polymorphism, Multigene family, Pyrrolidone carboxylic acid NM_000608 ORM2 orosomucoid 1 Glycoprotein, Plasma, Acute phase, 1930 5898 Signal, Lipocalin, Multigene family, Polymorphism, Pyrrolidone carboxylic acid NM_000631 NCF4 neutrophil cytosolic SH3 domain, Alternative splicing, 1931 5899 factor 4, 40 kDa 3D-structure NM_000632 ITGAM integrin, alpha M Integrin, Cell adhesion, Receptor, 1932 5900 (complement Glycoprotein, Transmembrane, component receptor Signal, 3D-structure, Repeat, 3, alpha; also known Magnesium, Calcium as CD11b (p170), macrophage antigen alpha polypeptide) NM_000633 BCL2 B-cell Proto-oncogene, Apoptosis, 1933 5901 CLL/lymphoma 2 Alternative splicing, Transmembrane, Mitochondrion, Phosphorylation, Chromosomal translocation, Polymorphism, Disease mutation, 3D-structure NM_000634 IL8RA interleukin 8 G-protein coupled receptor, 1934 5902 receptor, alpha Transmembrane, Glycoprotein, Chemotaxis, Polymorphism, 3D- structure, Receptor NM_000651 CR1 complement Complement pathway, Glycoprotein, 1935 5903 component (3b/4b) Transmembrane, Repeat, Signal, receptor 1, including Receptor, Sushi, Blood group Knops blood group antigen, Polymorphism, Pyrrolidone system carboxylic acid, 3D-structure NM_000655 SELL selectin L EGF-like domain, Cell adhesion, 1936 5904 (lymphocyte Transmembrane, Glycoprotein, adhesion molecule Lectin, Selectin, Signal, Sushi, 1) Repeat, 3D-structure NM_000671 ADH5 alcohol Oxidoreductase, Zinc, Metal-binding, 1937 5905 dehydrogenase 5 NAD, Multigene family, Acetylation, (class III), chi 3D-structure polypeptide NM_000675 ADORA2A adenosine A2a G-protein coupled receptor, 1938 5906 receptor Transmembrane, Glycoprotein, 3D- structure, Polymorphism NM_000688 ALAS1 aminolevulinate, Heme biosynthesis, Transferase, 1939 5907 delta-, synthase 1 Acyltransferase, Mitochondrion, Transit peptide, Pyridoxal phosphate, Multigene family NM_000690 ALDH2 aldehyde Oxidoreductase, NAD, 1940 5908 dehydrogenase 2 Mitochondrion, Transit peptide, family Polymorphism, 3D-structure (mitochondrial) NM_000694 ALDH3B1 aldehyde Oxidoreductase, NAD 1941 5909 dehydrogenase 3 family, member B1 NM_000698 ALOX5 arachidonate 5- Oxidoreductase, Dioxygenase, Iron, 1942 5910 lipoxygenase Leukotriene biosynthesis, Calcium NM_000701 ATP1A1 ATPase, Na+/K+ Hydrolase, Sodium/potassium 1943 5911 transporting, alpha 1 transport, Transmembrane, polypeptide Phosphorylation, Magnesium, Metal- binding, ATP-binding, Multigene family, Alternative splicing NM_000712 BLVRA biliverdin reductase A Oxidoreductase, NAD, NADP, Zinc, 1944 5912 Polymorphism NM_000714 BZRP benzodiazapine Mitochondrion, Receptor, 1945 5913 receptor (peripheral) Transmembrane, Polymorphism NM_000717 CA4 carbonic anhydrase GPI-anchor, Membrane, Lyase, Zinc, 1946 5914 IV Signal, 3D-structure, Lipoprotein NM_000718 CACNA1B calcium channel, Ionic channel, Transmembrane, Ion 1947 5915 voltage-dependent, transport, Voltage-gated channel, L type, alpha 1B Calcium channel, Glycoprotein, subunit Repeat, Multigene family, Calcium- binding, Phosphorylation, ATP- binding, Alternative splicing NM_000732 CD3D CD3D antigen, delta Immunoglobulin domain, T-cell, 1948 5916 polypeptide (TiT3 Receptor, Transmembrane, complex) Glycoprotein, Signal NM_000734 CD3Z CD3Z antigen, zeta T-cell, Receptor, Transmembrane, 1949 5917 polypeptide (TiT3 Signal, Repeat, Alternative splicing, complex) Phosphorylation, 3D-structure NM_000748 CHRNB2 cholinergic receptor, Postsynaptic membrane, Ionic 1950 5918 nicotinic, beta channel, Glycoprotein, Signal, polypeptide 2 Transmembrane, Multigene family, (neuronal) Disease mutation, Epilepsy NM_000749 CHRNB3 cholinergic receptor, Postsynaptic membrane, Ionic 1951 5919 nicotinic, beta channel, Glycoprotein, Signal, polypeptide 3 Transmembrane, Multigene family NM_000752 LTB4R leukotriene B4 Apoptosis, 3D-structure, RNA- 1952 5920 receptor 2 binding, Repeat, G-protein coupled receptor, Transmembrane, Glycoprotein NM_000757 CSF1 colony stimulating Cytokine, Growth factor, 1953 5921 factor 1 Glycoprotein, Proteoglycan, (macrophage) Transmembrane, Signal, Alternative splicing, 3D-structure NM_000760 CSF3R colony stimulating Cell adhesion, Receptor, Repeat, 1954 5922 factor 3 receptor Signal, Transmembrane, (granulocyte) Immunoglobulin domain, Glycoprotein, Alternative splicing, Polymorphism, 3D-structure NM_000778 CYP4A11 cytochrome P450, Heme, Monooxygenase, 1955 5923 family 4, subfamily Oxidoreductase, Electron transport, A, polypeptide 11 Membrane, Microsome, Endoplasmic reticulum, Polymorphism NM_000801 FKBP1A FK506 binding Isomerase, Rotamase, 3D-structure 1956 5924 protein 1A, 12 kDa NM_000804 FOLR3 folate receptor 3 Receptor, Glycoprotein, Signal, 1957 5925 (gamma) Folate-binding, Multigene family, Alternative splicing NM_000819 GART phosphoribosylglycinamide Multifunctional enzyme, Purine 1958 5926 formyltransferase, biosynthesis, Ligase, Transferase, phosphoribosylglycinamide Alternative splicing, Polymorphism synthetase, phosphoribosylaminoimidazole synthetase NM_000846 GSTA2 glutathione S- Transferase, Multigene family, 1959 5927 transferase A2 Polymorphism, 3D-structure NM_000856 GUCY1A3 guanylate cyclase 1, Lyase, cGMP biosynthesis, 1960 5928 soluble, alpha 3 Multigene family NM_000857 GUCY1B3 guanylate cyclase 1, Lyase, cGMP biosynthesis, 1961 5929 soluble, beta 3 Alternative splicing NM_000871 HTR6 5-hydroxytryptamine G-protein coupled receptor, 1962 5930 (serotonin) receptor 6 Transmembrane, Glycoprotein, Multigene family NM_000876 IGF2R insulin-like growth Transmembrane, Transport, 1963 5931 factor 2 receptor Glycoprotein, Repeat, Receptor, Lysosome, Signal, Polymorphism, 3D-structure NM_000877 IL1R1 interleukin 1 Receptor, Repeat, Signal, 1964 5932 receptor, type I Transmembrane, Immunoglobulin domain, Glycoprotein, Phosphorylation, 3D-structure NM_000878 IL2RB interleukin 2 Receptor, Transmembrane, 1965 5933 receptor, beta Glycoprotein, Signal, 3D-structure NM_000883 IMPDH1 IMP (inosine Oxidoreductase, NAD, GMP 1966 5934 monophosphate) biosynthesis, Purine biosynthesis, dehydrogenase 1 Multigene family, Repeat, CBS domain, Alternative splicing, Vision, Retinitis pigmentosa, Disease mutation NM_000895 LTA4H leukotriene A4 Multifunctional enzyme, Hydrolase, 1967 5935 hydrolase Leukotriene biosynthesis, Metalloprotease, Metal-binding, Zinc, 3D-structure NM_000903 NQO1 NAD(P)H Oxidoreductase, NAD, NADP, 1968 5936 dehydrogenase, Flavoprotein, FAD, Multigene family, quinone 1 Polymorphism, 3D-structure NM_000904 NQO2 NAD(P)H Oxidoreductase, Flavoprotein, FAD, 1969 5937 dehydrogenase, Multigene family, Zinc, 3D-structure quinone 2 NM_000918 P4HB procollagen-proline, Redox-active center, Isomerase, 1970 5938 2-oxoglutarate 4- Endoplasmic reticulum, Repeat, dioxygenase (proline Signal, 3D-structure, Hypothetical 4-hydroxylase), beta protein polypeptide (protein disulfide isomerase; thyroid hormone binding protein p55) NM_000952 PTAFR platelet-activating G-protein coupled receptor, 1971 5939 factor receptor Transmembrane, Glycoprotein, Chemotaxis, Polymorphism, Hypothetical protein NM_000954 PTGDS prostaglandin D2 Isomerase, Prostaglandin 1972 5940 synthase 21 kDa biosynthesis, Transport, (brain) Glycoprotein, Signal, Membrane, Lipocalin, Polymorphism NM_000963 PTGS2 prostaglandin- Oxidoreductase, Dioxygenase, 1973 5941 endoperoxide Peroxidase, Glycoprotein, synthase 2 Prostaglandin biosynthesis, Heme, (prostaglandin G/H Iron, Signal, Membrane, synthase and Polymorphism cyclooxygenase) NM_000966 RARG retinoic acid Receptor, Transcription regulation, 1974 5942 receptor, gamma DNA-binding, Nuclear protein, Zinc- finger, Multigene family, Alternative splicing, 3D-structure NM_000969 RPL5 ribosomal protein L5 Ribosomal protein, rRNA-binding, 1975 5943 Hydrolase, Metalloprotease, Aminopeptidase, Zinc, Nuclear protein NM_000985 RPL17 ribosomal protein Hypothetical protein, Ribosomal 1976 5944 L17 protein NM_000992 RPL29 ribosomal protein Methylation, Ribosomal protein, 1977 5945 L29 Repeat, Heparin-binding NM_000995 RPL34 ribosomal protein Ribosomal protein 1978 5946 L34 NM_001006 RPS3A ribosomal protein Ribosomal protein 1979 5947 S3A NM_001017 RPS13 ribosomal protein Ribosomal protein 1980 5948 S13 NM_001048 SST somatostatin Cleavage on pair of basic residues, 1981 5949 Hormone, Signal, Pharmaceutical NM_001051 SSTR3 somatostatin G-protein coupled receptor, 1982 5950 receptor 3 Transmembrane, Glycoprotein, Multigene family, Polymorphism NM_001052 SSTR4 somatostatin G-protein coupled receptor, 1983 5951 receptor 4 Transmembrane, Glycoprotein, Multigene family, Lipoprotein, Palmitate, Phosphorylation, Polymorphism NM_001054 SULT1A2 sulfotransferase Transferase, Steroid metabolism, 1984 5952 family, cytosolic, 1A, Polymorphism phenol-preferring, member 2 NM_001055 SULT1A1 sulfotransferase Transferase, Catecholamine 1985 5953 family, cytosolic, 1A, metabolism, Steroid metabolism, phenol-preferring, Polymorphism member 1 NM_001060 TBXA2R thromboxane A2 G-protein coupled receptor, 1986 5954 receptor Transmembrane, Glycoprotein, Disease mutation, Alternative splicing, Polymorphism, 3D- structure, Hypothetical protein, Metal-binding, Nuclear protein, Zinc, Zinc-finger NM_001062 TCN1 transcobalamin I Transport, Cobalt transport, 1987 5955 (vitamin B12 binding Glycoprotein, Signal protein, R binder family) NM_001064 TKT transketolase Transferase, Thiamine 1988 5956 (Wernicke-Korsakoff pyrophosphate, Calcium-binding syndrome) NM_001065 TNFRSF1A tumor necrosis factor Receptor, Apoptosis, 1989 5957 receptor superfamily, Transmembrane, Glycoprotein, member 1A Repeat, Signal, Disease mutation, Polymorphism, 3D-structure NM_001066 TNFRSF1B tumor necrosis factor Receptor, Apoptosis, 1990 5958 receptor superfamily, Transmembrane, Glycoprotein, member 1B Repeat, Signal, Phosphorylation, Pharmaceutical, Polymorphism, 3D- structure NM_001082 CYP4F2 cytochrome P450, Heme, Monooxygenase, 1991 5959 family 4, subfamily Oxidoreductase, Electron transport, F, polypeptide 2 Membrane, Microsome, Endoplasmic reticulum, Polymorphism, NADP NM_001087 AAMP angio-associated, Repeat, WD repeat 1992 5960 migratory cell protein NM_001089 ABCA3 ATP-binding ATP-binding, Transport, 1993 5961 cassette, sub-family Transmembrane A (ABC1), member 3 NM_001090 ABCF1 ATP-binding ATP-binding 1994 5962 cassette, sub-family F (GCN20), member 1 NM_001091 ABP1 amiloride binding Signal, Glycoprotein, 1995 5963 protein 1 (amine Oxidoreductase, Copper, Heparin- oxidase (copper- binding, TPQ, Alternative splicing, containing)) Polymorphism, Metal-binding NM_001099 ACPP acid phosphatase, Hydrolase, Glycoprotein, Signal, 3D- 1996 5964 prostate structure NM_001101 ACTB actin, beta Hypothetical protein, Structural 1997 5965 protein, Multigene family, Methylation, Acetylation, Cytoskeleton, 3D-structure NM_001102 ACTN1 actinin, alpha 1 Cytoskeleton, Actin-binding, 1998 5966 Calcium-binding, Repeat, Multigene family, Phosphorylation NM_001105 ACVR1 activin A receptor, Receptor, Transferase, 1999 5967 type I Serine/threonine-protein kinase, ATP-binding, Transmembrane, Glycoprotein, Signal NM_001107 ACYP1 acylphosphatase 1, Hydrolase, Acetylation, Multigene 2000 5968 erythrocyte family (common) type NM_001109 ADAM8 a disintegrin and Hydrolase, Metalloprotease, Zinc, 2001 5969 metalloproteinase Signal, Glycoprotein, domain 8 Transmembrane, Antigen, EGF-like domain NM_001120 TETRAN tetracycline Transmembrane 2002 5970 transporter-like protein NM_001129 AEBP1 AE binding protein 1 Carboxypeptidase 2003 5971 NM_001140 ALOX15 arachidonate 15- Oxidoreductase, Dioxygenase, Iron, 2004 5972 lipoxygenase Leukotriene biosynthesis NM_001150 ANPEP alanyl (membrane) Angiogenesis, Hydrolase, 2005 5973 aminopeptidase Aminopeptidase, Metalloprotease, (aminopeptidase N, Zinc, Signal-anchor, aminopeptidase M, Transmembrane, Glycoprotein, microsomal Sulfation, Polymorphism aminopeptidase, CD13, p150) NM_001152 SLC25A5 solute carrier family Mitochondrion, Inner membrane, 2006 5974 25 (mitochondrial Repeat, Transmembrane, Transport, carrier; adenine Multigene family nucleotide translocator), member 5 NM_001153 ANXA4 annexin A4 Annexin, Calcium/phospholipid- 2007 5975 binding, Repeat NM_001155 ANXA6 annexin A6 Annexin, Calcium/phospholipid- 2008 5976 binding, Repeat, Acetylation, Phosphorylation, 3D-structure NM_001157 ANXA11 annexin A11 Annexin, Calcium/phospholipid- 2009 5977 binding, Repeat, Polymorphism NM_001172 ARG2 arginase, type II Urea cycle, Arginine metabolism, 2010 5978 Hydrolase, Manganese, Transit peptide, Mitochondrion, Receptor, Transmembrane, Transport, Protein transport, Coiled coil, Alternative splicing NM_001175 ARHGDIB Rho GDP GTPase activation, 3D-structure 2011 5979 dissociation inhibitor (GDI) beta NM_001181 ASGR2 asialoglycoprotein Lectin, Glycoprotein, Receptor, 2012 5980 receptor 2 Endocytosis, Transmembrane, Calcium, Signal-anchor, Phosphorylation, Alternative splicing NM_001182 ALDH7A1 aldehyde Oxidoreductase, NAD 2013 5981 dehydrogenase 7 family, member A1 NM_001183 ATP6IP1 ATPase, H+ Hypothetical protein, ATP synthesis, 2014 5982 transporting, Hydrogen ion transport, Hydrolase, lysosomal accessory ATP-binding, Transmembrane, protein 1 Glycoprotein, Signal NM_001184 ATR ataxia telangiectasia Kinase, Transferase 2015 5983 and Rad3 related NM_001196 BID BH3 interacting Apoptosis, 3D-structure 2016 5984 domain death agonist NM_001199 BMP1 bone morphogenetic Growth factor, Cytokine, Repeat, 2017 5985 protein 1 Osteogenesis, Chondrogenesis, Hydrolase, Metalloprotease, EGF- like domain, Zinc, Calcium, Signal, Glycoprotein, Zymogen, Alternative splicing, Collagen NM_001206 BTEB1 basic transcription Transcription regulation, DNA- 2018 5986 element binding binding, Nuclear protein, Repeat, protein 1 Zinc-finger, Metal-binding NM_001207 BTF3 basic transcription Transcription regulation, Nuclear 2019 5987 factor 3 protein, Alternative splicing NM_001208 BTF3L1 basic transcription Transcription regulation, Nuclear 2020 5988 factor 3, like 1 protein NM_001212 C1QBP complement Mitochondrion, Transit peptide, 3D- 2021 5989 component 1, q structure, Hypothetical protein subcomponent binding protein NM_001222 CAMK2G calcium/calmodulin- Alternative splicing 2022 5990 dependent protein kinase (CaM kinase) II gamma NM_001237 CCNA2 cyclin A2 Cyclin, Cell cycle, Cell division, 2023 5991 Mitosis, 3D-structure NM_001252 TNFSF7 tumor necrosis factor Cytokine, Transmembrane, 2024 5992 (ligand) superfamily, Glycoprotein, Signal-anchor, Antigen member 7 NM_001256 CDC27 cell division cycle 27 Repeat, TPR repeat, Nuclear 2025 5993 protein, Polymorphism NM_001259 CDK6 cyclin-dependent Transferase, Serine/threonine- 2026 5994 kinase 6 protein kinase, ATP-binding, Cell cycle, Cell division, Phosphorylation, 3D-structure NM_001266 CES1 carboxylesterase 1 Glycoprotein, Hydrolase, Serine 2027 5995 (monocyte/macrophage esterase, Endoplasmic reticulum, serine esterase Signal, Multigene family, 1) Polymorphism, Hypothetical protein NM_001276 CHI3L1 chitinase 3-like 1 Glycoprotein, Signal, 3D-structure 2028 5996 (cartilage glycoprotein-39) NM_001282 AP2B1 adaptor-related Hypothetical protein, Coated pits, 2029 5997 protein complex 2, 3D-structure beta 1 subunit NM_001284 AP3S1 adaptor-related Golgi stack, Protein transport, 2030 5998 protein complex 3, Transport sigma 1 subunit NM_001286 CLCN6 chloride channel 6 Ionic channel, Ion transport, Chloride 2031 5999 channel, Chloride, Voltage-gated channel, Transmembrane, CBS domain, Repeat, Alternative splicing NM_001288 CLIC1 chloride intracellular Ionic channel, Ion transport, Chloride 2032 6000 channel 1 channel, Chloride, Voltage-gated channel, Nuclear protein, 3D- structure NM_001292 CLK3 CDC-like kinase 3 Transferase, Serine/threonine- 2033 6001 protein kinase, ATP-binding, Tyrosine-protein kinase, Phosphorylation, Nuclear protein, Alternative splicing NM_001293 CLNS1A chloride channel, Nuclear protein, Polymorphism 2034 6002 nucleotide-sensitive, 1A NM_001294 CLPTM1 cleft lip and palate Transmembrane 2035 6003 associated transmembrane protein 1 NM_001305 CLDN4 claudin 4 Tight junction, Transmembrane, 2036 6004 Williams-Beuren syndrome NM_001313 CRMP1 collapsin response Repeat, WD repeat 2037 6005 mediator protein 1 NM_001315 MAPK14 mitogen-activated ATP-binding, Kinase, Transferase, 2038 6006 protein kinase 14 Serine/threonine-protein kinase, Phosphorylation, Alternative splicing, 3D-structure NM_001317 CSH1 chorionic Chorion, Hormone, Placenta, 2039 6007 somatomammotropin Multigene family, Signal hormone 1 (placental lactogen) NM_001325 CSTF2 cleavage stimulation RNA-binding, Repeat, 2040 6008 factor, 3′ pre-RNA, Phosphorylation, Nuclear protein subunit 2, 64 kDa NM_001331 CTNND1 catenin (cadherin- Cytoskeleton, Structural protein, 2041 6009 associated protein), Phosphorylation, Repeat, Cell delta 1 adhesion, Coiled coil, Nuclear protein, Alternative splicing NM_001338 CXADR coxsackie virus and Immunoglobulin domain, Receptor, 2042 6010 adenovirus receptor Transmembrane, Glycoprotein, Signal, Repeat, 3D-structure NM_001346 DGKG diacylglycerol Transferase, Kinase, Calcium- 2043 6011 kinase, gamma binding, Phorbol-ester binding, 90 kDa Repeat, Multigene family, Alternative splicing NM_001357 DDX9 DEAH (Asp-Glu-Ala- Helicase, RNA-binding, DNA- 2044 6012 His) box polypeptide 9 binding, Repeat, Nuclear protein, ATP-binding NM_001358 DDX15 DEAH (Asp-Glu-Ala- mRNA processing, mRNA splicing, 2045 6013 His) box polypeptide Helicase, ATP-binding, Nuclear 15 protein NM_001363 DKC1 dyskeratosis Telomere, RNA-binding, Nuclear 2046 6014 congenita 1, protein, Disease mutation dyskerin NM_001381 DOK1 docking protein 1, Phosphorylation, Alternative splicing 2047 6015 62 kDa (downstream of tyrosine kinase 1) NM_001383 DPH2L1 diptheria toxin 2048 6016 resistance protein required for diphthamide biosynthesis-like 1 (S. cerevisiae) NM_001388 DRG2 developmentally GTP-binding 2049 6017 regulated GTP binding protein 2 NM_001406 EFNB3 ephrin-B3 Developmental protein, 2050 6018 Neurogenesis, Transmembrane, Glycoprotein, Signal, Polymorphism NM_001415 EIF2S3 eukaryotic Initiation factor, Protein biosynthesis, 2051 6019 translation initiation GTP-binding, Polymorphism factor 2, subunit 3 gamma, 52 kDa NM_001419 ELAVL1 ELAV (embryonic RNA-binding, Repeat 2052 6020 lethal, abnormal vision, Drosophila)- like 1 (Hu antigen R) NM_001421 ELF4 E74-like factor 4 (ets 2053 6021 domain transcription factor) NM_001423 EMP1 epithelial membrane Transmembrane, Glycoprotein 2054 6022 protein 1 NM_001431 EPB41L2 erythrocyte Hypothetical protein, Structural 2055 6023 membrane protein protein, Cytoskeleton, Actin-binding band 4.1-like 2 NM_001432 EREG epiregulin Angiogenesis, Growth factor, 2056 6024 Mitogen, Glycoprotein, EGF-like domain, Transmembrane, Signal NM_001440 EXTL3 exostoses (multiple)- Transferase, Glycosyltransferase, 2057 6025 like 3 Endoplasmic reticulum, Transmembrane, Signal-anchor, Glycoprotein NM_001444 FABP5 fatty acid binding Transport, Lipid-binding, 3D- 2058 6026 protein 5 (psoriasis- structure associated) NM_001449 FHL1 four and a half LIM Coiled coil, Transcription regulation, 2059 6027 domains 1 Nuclear protein, Disease mutation, Anhidrotic ectodermal dysplasia, Repeat, LIM domain, Metal-binding, Zinc, Developmental protein, Differentiation, Zinc-finger NM_001455 FOXO3A forkhead box O3A Transcription regulation, DNA- 2060 6028 binding, Nuclear protein, Apoptosis, Chromosomal translocation, Proto- oncogene, Phosphorylation NM_001456 FLNA filamin A, alpha Cytoskeleton, Actin-binding, Repeat, 2061 6029 (actin binding protein Phosphorylation, Polymorphism, 280) Disease mutation, Multigene family, Hypothetical protein NM_001462 FPRL1 formyl peptide G-protein coupled receptor, 2062 6030 receptor-like 1 Transmembrane, Glycoprotein, Chemotaxis, Repeat, WD repeat NM_001465 FYB FYN binding protein SH3 domain, Phosphorylation, 2063 6031 (FYB-120/130) Nuclear protein, Coiled coil, Alternative splicing NM_001467 G6PT1 solute carrier family Transmembrane, Transport, Sugar 2064 6032 37 (glycerol-6- transport, Endoplasmic reticulum, phosphate Alternative splicing, Glycogen transporter), storage disease, Disease mutation member 4 NM_001469 G22P1 thyroid autoantigen Helicase, Nuclear protein, DNA- 2065 6033 70 kDa (Ku antigen) binding, Phosphorylation, Antigen, Systemic lupus erythematosus, Acetylation, 3D-structure NM_001478 GALGT UDP-N-acetyl-alpha- Hypothetical protein, Transferase, 2066 6034 D-galactosamine:(N- Glycosyltransferase, acetylneuraminyl)- Transmembrane, Signal-anchor, galactosylglucosylceramide Golgi stack, Glycoprotein, N- Polymorphism acetylgalactosaminyl transferase (GalNAc-T) NM_001482 GATM glycine Transferase, Mitochondrion, Transit 2067 6035 amidinotransferase peptide, 3D-structure, Alternative (L-arginine:glycine splicing amidinotransferase) NM_001483 GBAS glioblastoma 2068 6036 amplified sequence NM_001487 GCN5L1 GCN5 general 2069 6037 control of amino-acid synthesis 5-like 1 (yeast) NM_001493 GDI1 GDP dissociation GTPase activation, Disease 2070 6038 inhibitor 1 mutation NM_001500 GMDS GDP-mannose 4,6- Lyase, NADP 2071 6039 dehydratase NM_001503 GPLD1 glycosylphosphatidyl Hydrolase, Glycoprotein, Signal, 2072 6040 inositol specific Hypothetical protein phospholipase D1 NM_001504 CXCR3 chemokine (C—X—C G-protein coupled receptor, 2073 6041 motif) receptor 3 Transmembrane, Glycoprotein, Antigen, Polymorphism NM_001517 GTF2H4 general transcription Transcription regulation, DNA repair, 2074 6042 factor IIH, Nuclear protein polypeptide 4, 52 kDa NM_001518 GTF2I general transcription Transcription regulation, DNA- 2075 6043 factor II, i binding, Nuclear protein, Phosphorylation, Repeat, Williams- Beuren syndrome, Alternative splicing NM_001519 BRF1 BRF1 homolog, Transcription regulation, Activator, 2076 6044 subunit of RNA Nuclear protein, Repeat, Zinc-finger, polymerase III Metal-binding, Zinc, Alternative transcription splicing, Hypothetical protein initiation factor IIIB (S. cerevisiae) NM_001520 GTF3C1 general transcription 2077 6045 factor IIIC, polypeptide 1, alpha 220 kDa NM_001528 HGFAC HGF activator Hydrolase, Glycoprotein, Plasma, 2078 6046 Serine protease, Kringle, Signal, EGF-like domain, Repeat, Zymogen NM_001531 MR1 major MHC, Glycoprotein, Transmembrane 2079 6047 histocompatibility complex, class I- related NM_001536 HRMT1L2 HMT1 hnRNP Transferase, Methyltransferase, 2080 6048 methyltransferase- Nuclear protein, Alternative splicing like 2 (S. cerevisiae) NM_001538 HSF4 F-box and leucine- Transcription regulation, Nuclear 2081 6049 rich repeat protein 8 protein, DNA-binding, Activator, Repressor, Heat shock, Multigene family, Alternative splicing NM_001539 DNAJA1 DnaJ (Hsp40) Chaperone, Repeat, Zinc, Metal- 2082 6050 homolog, subfamily binding, Prenylation, Lipoprotein, A, member 1 Multigene family NM_001550 IFRD1 interferon-related 2083 6051 developmental regulator 1 NM_001551 IGBP1 immunoglobulin B-cell activation, Phosphorylation 2084 6052 (CD79A) binding protein 1 NM_001554 CYR61 cysteine-rich, Plasmid, Chemotaxis, Cell adhesion, 2085 6053 angiogenic inducer, Growth factor binding, Heparin- 61 binding, Signal NM_001557 IL8RB interleukin 8 G-protein coupled receptor, 2086 6054 receptor, beta Transmembrane, Glycoprotein, Chemotaxis, Polymorphism, Receptor NM_001558 IL10RA interleukin 10 Receptor, Transmembrane, 2087 6055 receptor, alpha Glycoprotein, Signal, Polymorphism, 3D-structure NM_001567 INPPL1 inositol DNA repair 2088 6056 polyphosphate phosphatase-like 1 NM_001572 IRF7 interferon regulatory Transcription regulation, DNA- 2089 6057 factor 7 binding, Nuclear protein, Activator, Alternative splicing, Collagen NM_001607 ACAA1 acetyl-Coenzyme A Acyltransferase, Transferase, Fatty 2090 6058 acyltransferase 1 acid metabolism, Peroxisome, (peroxisomal 3- Transit peptide, Polymorphism oxoacyl-Coenzyme A thiolase) NM_001618 ADPRT ADP- Transferase, Glycosyltransferase, 2091 6059 ribosyltransferase NAD, DNA-binding, Nuclear protein, (NAD+; poly (ADP- ADP-ribosylation, Zinc-finger, Zinc, ribose) polymerase) Polymorphism NM_001619 ADRBK1 adrenergic, beta, Kinase, Receptor, Transferase, 2092 6060 receptor kinase 1 Serine/threonine-protein kinase, ATP-binding, Multigene family, 3D- structure NM_001621 AHR aryl hydrocarbon Cell cycle, Transcription regulation, 2093 6061 receptor Activator, Receptor, DNA-binding, Nuclear protein, Repeat, Polymorphism NM_001628 AKR1B1 aldo-keto reductase Oxidoreductase, NADP, Acetylation, 2094 6062 family 1, member B1 3D-structure, Polymorphism (aldose reductase) NM_001629 ALOX5AP arachidonate 5- Transmembrane, Leukotriene 2095 6063 lipoxygenase- biosynthesis activating protein NM_001632 ALPP alkaline Hydrolase, Zinc, Magnesium, 2096 6064 phosphatase, Phosphorylation, Transmembrane, placental (Regan Placenta, Multigene family, isozyme) Glycoprotein, GPI-anchor, Signal, 3D-structure, Lipoprotein NM_001634 AMD1 adenosylmethionine Spermidine biosynthesis, Lyase, 2097 6065 decarboxylase 1 Decarboxylase, Pyruvate, Zymogen, 3D-structure NM_001637 AOAH acyloxyacyl Hydrolase, Signal, Transmembrane, 2098 6066 hydrolase Glycoprotein (neutrophil) NM_001643 APOA2 apolipoprotein A-II Transport, Lipid transport, HDL, 2099 6067 Signal, Pyrrolidone carboxylic acid, 3D-structure NM_001654 ARAF1 v-raf murine Transferase, Serine/threonine- 2100 6068 sarcoma 3611 viral protein kinase, Proto-oncogene, oncogene homolog 1 Metal-binding, Zinc, ATP-binding, Phorbol-ester binding, Kinase NM_001657 AREG amphiregulin Glycoprotein, Cytokine, Growth 2101 6069 (schwannoma- factor, EGF-like domain, Signal, derived growth Transmembrane factor) NM_001662 ARF5 ADP-ribosylation GTP-binding, Multigene family, 2102 6070 factor 5 Myristate, Protein transport, Golgi stack, Lipoprotein NM_001665 ARHG ras homolog gene GTP-binding, Prenylation, 2103 6071 family, member G Lipoprotein (rho G) NM_001667 ARL2 sorting nexin 15 GTP-binding, Multigene family, 2104 6072 Hypothetical protein, Transport, Protein transport, Alternative splicing NM_001670 ARVCF armadillo repeat Hypothetical protein, Cell adhesion, 2105 6073 gene deletes in Cytoskeleton, Structural protein, velocardiofacial Repeat, Coiled coil, Alternative syndrome splicing NM_001671 ASGR1 asialoglycoprotein Lectin, Glycoprotein, Receptor, 2106 6074 receptor 1 Endocytosis, Transmembrane, Calcium, Signal-anchor, Phosphorylation, 3D-structure NM_001677 ATP1B1 ATPase, Na+/K+ Transferase, Kinase, ATP-binding, 2107 6075 transporting, beta 1 Sodium/potassium transport, polypeptide Transmembrane, Glycoprotein, Multigene family, Signal-anchor, Alternative splicing NM_001678 ATP1B2 ATPase, Na+/K+ Sodium/potassium transport, 2108 6076 transporting, beta 2 Transmembrane, Glycoprotein, polypeptide Multigene family, Signal-anchor NM_001679 ATP1B3 ATPase, Na+/K+ Sodium/potassium transport, 2109 6077 transporting, beta 3 Transmembrane, Glycoprotein, polypeptide Multigene family, Signal-anchor NM_001681 ATP2A2 ATPase, Ca++ Hydrolase, Calcium transport, 2110 6078 transporting, cardiac Transmembrane, Phosphorylation, muscle, slow twitch 2 ATP-binding, Metal-binding, Magnesium, Calcium-binding, Multigene family, Alternative splicing, Disease mutation, Epilepsy NM_001693 ATP6V1B2 ATPase, H+ Hydrolase, ATP synthesis, Hydrogen 2111 6079 transporting, ion transport, Multigene family lysosomal 56/58 kDa, V1 subunit B, isoform 2 NM_001706 BCL6 B-cell Nuclear protein, Transcription 2112 6080 CLL/lymphoma 6 regulation, Activator, DNA-binding, (zinc finger protein Zinc-finger, Metal-binding, Repeat, 51) Proto-oncogene, Chromosomal translocation, Polymorphism NM_001712 CEACAM1 carcinoembryonic Alternative splicing, Immunoglobulin 2113 6081 antigen-related cell domain, Signal, Transmembrane, adhesion molecule 1 Glycoprotein, Repeat, Pyrrolidone (biliary glycoprotein) carboxylic acid, Hypothetical protein NM_001714 BICD1 Bicaudal D homolog Golgi stack, Coiled coil, Alternative 2114 6082 1 (Drosophila) splicing NM_001716 BLR1 Burkitt lymphoma B-cell activation, G-protein coupled 2115 6083 receptor 1, GTP receptor, Transmembrane, binding protein Glycoprotein, Alternative splicing, (chemokine (C—X—C Polymorphism motif) receptor 5) NM_001721 BMX BMX non-receptor Transferase, Tyrosine-protein 2116 6084 tyrosine kinase kinase, Phosphorylation, ATP- binding, SH3 domain, SH2 domain NM_001725 BPI bactericidal/permeability- Antibiotic, Signal, Transmembrane, 2117 6085 increasing Glycoprotein, 3D-structure protein NM_001728 BSG basigin (OK blood Immunoglobulin domain, 2118 6086 group) Transmembrane, Glycoprotein, Signal, Antigen, Blood group antigen, Polymorphism NM_001730 KLF5 Kruppel-like factor 5 Transcription regulation, DNA- 2119 6087 (intestinal) binding, Nuclear protein, Repeat, Zinc-finger, Metal-binding, Activator NM_001731 BTG1 B-cell translocation Proto-oncogene, Chromosomal 2120 6088 gene 1, anti- translocation proliferative NM_001736 C5R1 complement G-protein coupled receptor, 2121 6089 component 5 Transmembrane, Glycoprotein, receptor 1 (C5a Sulfation, Chemotaxis ligand) NM_001745 CAMLG calcium modulating Transmembrane 2122 6090 ligand NM_001747 CAPG capping protein Nuclear protein, Actin-binding, 2123 6091 (actin filament), Repeat, 3D-structure, Actin capping gelsolin-like NM_001749 CAPNS1 calpain, small Calcium-binding, Repeat, 3D- 2124 6092 subunit 1 structure NM_001750 CAST calpastatin Repeat, Thiol protease inhibitor, 2125 6093 Alternative splicing, Phosphorylation, Signal transduction inhibitor NM_001767 CD2 CD2 antigen (p50), Immunoglobulin domain, T-cell, 2126 6094 sheep red blood cell Glycoprotein, Antigen, receptor Transmembrane, Cell adhesion, Repeat, Signal, Polymorphism, 3D- structure NM_001769 CD9 CD9 antigen (p24) Glycoprotein, Antigen, 2127 6095 Transmembrane, Lipoprotein, Phosphorylation NM_001771 CD22 CD22 antigen Cell adhesion, Lectin, Antigen, 2128 6096 Transmembrane, Signal, Glycoprotein, Immunoglobulin domain, Repeat, Phosphorylation, Alternative splicing, Polymorphism NM_001773 CD34 CD34 antigen Cell adhesion, Antigen, Signal, 2129 6097 Transmembrane, Glycoprotein, Phosphorylation, Alternative splicing NM_001774 CD37 CD37 antigen Glycoprotein, Antigen, 2130 6098 Transmembrane, Hypothetical protein NM_001776 ENTPD1 ectonucleoside Hydrolase, Transmembrane, 2131 6099 triphosphate Antigen, Glycoprotein, Calcium, diphosphohydrolase 1 Magnesium, Alternative splicing, Lipoprotein, Palmitate NM_001777 CD47 CD47 antigen (Rh- Cell adhesion, Antigen, Signal, 2132 6100 related antigen, Transmembrane, Glycoprotein, integrin-associated Alternative splicing signal transducer) NM_001780 CD63 CD63 antigen Glycoprotein, Antigen, 2133 6101 (melanoma 1 Transmembrane, Lysosome antigen) NM_001781 CD69 CD69 antigen (p60, Antigen, Signal-anchor, 2134 6102 early T-cell Transmembrane, Lectin, activation antigen) Glycoprotein, Phosphorylation, 3D- structure NM_001800 CDKN2D cyclin-dependent Cell cycle, Anti-oncogene, Repeat, 2135 6103 kinase inhibitor 2D ANK repeat, 3D-structure (p19, inhibits CDK4) NM_001803 CDW52 CDW52 antigen Antigen, Signal, Glycoprotein, GPI- 2136 6104 (CAMPATH-1 anchor, Membrane, Polymorphism, antigen) Lipoprotein NM_001805 CEBPE CCAAT/enhancer Transcription regulation, Activator, 2137 6105 binding protein DNA-binding, Nuclear protein, (C/EBP), epsilon Phosphorylation NM_001806 CEBPG CCAAT/enhancer Transcription regulation, Activator, 2138 6106 binding protein DNA-binding, Nuclear protein (C/EBP), gamma NM_001808 CELL carboxyl ester lipase 2139 6107 pseudogene NM_001815 CEACAM3 carcinoembryonic Immunoglobulin domain, Antigen, 2140 6108 antigen-related cell Signal, Glycoprotein, adhesion molecule 3 Transmembrane, Alternative splicing, Polymorphism NM_001816 CEACAM8 carcinoembryonic Immunoglobulin domain, Antigen, 2141 6109 antigen-related cell Signal, Glycoprotein, GPI-anchor, adhesion molecule 8 Repeat, Polymorphism, Lipoprotein NM_001817 CEACAM4 carcinoembryonic Antigen 2142 6110 antigen-related cell adhesion molecule 4 NM_001828 CLC Charot-Leyden Hydrolase, Serine esterase, Lipid 2143 6111 crystal protein degradation, Galectin, Acetylation, 3D-structure, Polymorphism NM_001835 CLTCL1 clathrin, heavy Coated pits, Alternative splicing 2144 6112 polypeptide-like 1 NM_001838 CCR7 chemokine (C—C G-protein coupled receptor, 2145 6113 motif) receptor 7 Transmembrane, Glycoprotein, Signal NM_001839 CNN3 calponin 3, acidic Calmodulin-binding, Actin-binding, 2146 6114 Multigene family, Repeat NM_001853 COL9A3 collagen, type IX, Hypothetical protein, Collagen, 2147 6115 alpha 3 Extracellular matrix, Connective tissue, Repeat, Hydroxylation, Glycoprotein, Signal, Polymorphism NM_001882 CRHBP corticotropin Glycoprotein, Signal 2148 6116 releasing hormone binding protein NM_001889 CRYZ crystallin, zeta Oxidoreductase, NADP, Zinc 2149 6117 (quinone reductase) NM_001894 CSNK1E casein kinase 1, Transferase, Serine/threonine- 2150 6118 epsilon protein kinase, ATP-binding, Phosphorylation, Multigene family NM_001907 CTRL chymotrypsin-like Hydrolase, Protease, Serine 2151 6119 protease, Transferase, Serine/threonine-protein kinase, ATP-binding, Phosphorylation, Golgi stack, Nuclear protein, Glycoprotein, Zymogen, Signal NM_001909 CTSD cathepsin D Hydrolase, Aspartyl protease, 2152 6120 (lysosomal aspartyl Glycoprotein, Lysosome, Signal, protease) Zymogen, Polymorphism, Alzheimer's disease, 3D-structure NM_001911 CTSG cathepsin G Hydrolase, Serine protease, 2153 6121 Zymogen, Glycoprotein, Signal, Polymorphism, 3D-structure NM_001921 DCTD dCMP deaminase Hydrolase, Allosteric enzyme, 2154 6122 Nucleotide biosynthesis, Zinc NM_001925 DEFA4 defensin, alpha 4, Defensin, Antibiotic, Fungicide, 2155 6123 corticostatin Signal NM_001939 DRP2 dystrophin related Structural protein, Cytoskeleton, 2156 6124 protein 2 Repeat, Zinc-finger NM_001940 DRPLA dentatorubral- Triplet repeat expansion, 2157 6125 pallidoluysian Polymorphism, Epilepsy atrophy (atrophin-1) NM_001946 DUSP6 dual specificity Hydrolase, Polymorphism, 2158 6126 phosphatase 6 Alternative splicing, 3D-structure NM_001951 E2F5 E2F transcription Transcription regulation, Activator, 2159 6127 factor 5, p130- DNA-binding, Nuclear protein, binding Polymorphism NM_001953 ECGF1 endothelial cell Transferase, Glycosyltransferase, 2160 6128 growth factor 1 Growth factor, Chemotaxis, (platelet-derived) Angiogenesis, Repeat, Polymorphism, Disease mutation NM_001964 EGR1 early growth Transcription regulation, Activator, 2161 6129 response 1 DNA-binding, Nuclear protein, Repeat, Zinc-finger, Metal-binding NM_001965 EGR4 early growth Nuclear protein, Transcription 2162 6130 response 4 regulation, DNA-binding, Zinc-finger, Metal-binding, Repeat NM_001970 EIF5A eukaryotic Protein biosynthesis, Initiation factor, 2163 6131 translation initiation Hypusine, 3D-structure factor 5A NM_001972 ELA2 elastase 2, Hydrolase, Serine protease, 2164 6132 neutrophil Glycoprotein, Signal, 3D-structure, Disease mutation NM_001992 F2R coagulation factor II G-protein coupled receptor, 2165 6133 (thrombin) receptor Transmembrane, Glycoprotein, Signal, Blood coagulation, Phosphorylation, Polymorphism, 3D- structure, Receptor NM_001995 FACL1 fatty-acid-Coenzyme Ligase, Fatty acid metabolism, 2166 6134 A ligase, long-chain 2 Magnesium, Multigene family, Hypothetical protein NM_001996 FBLN1 fibulin 1 Signal, Alternative splicing, 2167 6135 Glycoprotein, Extracellular matrix, Repeat, EGF-like domain, Calcium- binding, Chromosomal translocation, Polymorphism, Hypothetical protein NM_001999 FBN2 fibrillin 2 (congenital Hypothetical protein, EGF-like 2168 6136 contractural domain, Extracellular matrix, arachnodactyly) Calcium-binding, Glycoprotein, Repeat, Signal, Multigene family, Disease mutation, Polymorphism NM_002000 FCAR Fc fragment of IgA, Receptor, Glycoprotein, 2169 6137 receptor for Transmembrane, IgA-binding protein, Immunoglobulin domain, Repeat, Signal, Alternative splicing NM_002003 FCN1 ficolin Lectin, Collagen, Repeat, 2170 6138 (collagen/fibrinogen Glycoprotein, Signal, Multigene domain containing) 1 family NM_002005 FES feline sarcoma Transferase, Tyrosine-protein 2171 6139 oncogene kinase, Proto-oncogene, ATP- binding, Phosphorylation, SH2 domain NM_002010 FGF9 fibroblast growth Growth factor, Differentiation, 2172 6140 factor 9 (glia- Mitogen, Heparin-binding, activating factor) Glycoprotein, 3D-structure NM_002013 FKBP3 FK506 binding Isomerase, Rotamase, Nuclear 2173 6141 protein 3, 25 kDa protein, 3D-structure NM_002014 FKBP4 FK506 binding Isomerase, Rotamase, Repeat, TPR 2174 6142 protein 4, 59 kDa repeat, Nuclear protein, Phosphorylation, 3D-structure NM_002017 FLI1 Friend leukemia Transcription regulation, Activator, 2175 6143 virus integration 1 DNA-binding, Nuclear protein, Alternative splicing, Proto-oncogene, Chromosomal translocation, 3D- structure NM_002018 FLII flightless I homolog Developmental protein, Repeat, 2176 6144 (Drosophila) Leucine-rich repeat NM_002029 FPR1 formyl peptide G-protein coupled receptor, 2177 6145 receptor 1 Transmembrane, Glycoprotein, Chemotaxis, Polymorphism NM_002032 FTH1 ferritin, heavy Transport, Ion transport, Ionic 2178 6146 polypeptide 1 channel, Chloride channel, Chloride, Calcium, Alternative splicing, Disease mutation, Polymorphism, Vision, Transmembrane, Phosphorylation, Iron storage, Metal- binding, 3D-structure NM_002033 FUT4 fucosyltransferase 4 Transferase, Glycosyltransferase, 2179 6147 (alpha (1, 3) Transmembrane, Glycoprotein, fucosyltransferase, Signal-anchor, Golgi stack myeloid-specific) NM_002035 FVT1 follicular lymphoma Proto-oncogene, Chromosomal 2180 6148 variant translocation 1 translocation, Oxidoreductase, Signal NM_002037 FYN FYN oncogene Hypothetical protein, ATP-binding, 2181 6149 related to SRC, SH3 domain, Transferase, Kinase, FGR, YES Tyrosine-protein kinase, Proto- oncogene, Phosphorylation, Myristate, SH2 domain, Palmitate, Lipoprotein, 3D-structure, Polymorphism NM_002046 GAPD glyceraldehyde-3- Glycolysis, NAD, Oxidoreductase, 2182 6150 phosphate Multigene family dehydrogenase NM_002051 GATA3 GATA binding Hypothetical protein, Transcription 2183 6151 protein 3 regulation, Activator, DNA-binding, Zinc-finger, Nuclear protein, T-cell, Alternative splicing NM_002061 GCLM glutamate-cysteine Ligase, Glutathione biosynthesis 2184 6152 ligase, modifier subunit NM_002064 GLRX glutaredoxin Redox-active center, Electron 2185 6153 (thioltransferase) transport, Acetylation, Polymorphism, 3D-structure NM_002068 GNA15 guanine nucleotide GTP-binding, Transducer, Multigene 2186 6154 binding protein (G family, ADP-ribosylation protein), alpha 15 (Gq class) NM_002069 GNAI1 guanine nucleotide Hypothetical protein, GTP-binding, 2187 6155 binding protein (G Transducer, ADP-ribosylation, protein), alpha Multigene family, Myristate, inhibiting activity Palmitate, Lipoprotein, 3D-structure polypeptide 1 NM_002070 GNAI2 guanine nucleotide GTP-binding, Transducer, ADP- 2188 6156 binding protein (G ribosylation, Multigene family, protein), alpha Myristate, Palmitate, Lipoprotein inhibiting activity polypeptide 2 NM_002073 GNAZ guanine nucleotide GTP-binding, Transducer, ADP- 2189 6157 binding protein (G ribosylation, Multigene family, protein), alpha z Lipoprotein, Palmitate, Myristate, polypeptide Membrane NM_002081 GPC1 glypican 1 Proteoglycan, Heparan sulfate, 2190 6158 Glycoprotein, Signal, GPI-anchor, Lipoprotein NM_002082 GPRK6 G protein-coupled Transferase, Serine/threonine- 2191 6159 receptor kinase 6 protein kinase, ATP-binding, Phosphorylation, Lipoprotein, Palmitate, Alternative splicing, Kinase, Receptor, Hypothetical protein NM_002086 GRB2 growth factor SH2 domain, SH3 domain, Repeat, 2192 6160 receptor-bound Alternative splicing, 3D-structure protein 2 NM_002087 GRN granulin Cytokine, Repeat, Glycoprotein, 2193 6161 Signal, Alternative splicing, Polymorphism, 3D-structure, Hypothetical protein NM_002092 GRSF1 G-rich RNA Hypothetical protein, RNA-binding, 2194 6162 sequence binding Repeat factor 1 NM_002093 GSK3B glycogen synthase Transferase, Serine/threonine- 2195 6163 kinase 3 beta protein kinase, ATP-binding, Wnt signaling pathway, Phosphorylation, Multigene family, Alternative splicing, 3D-structure NM_002096 GTF2F1 general transcription Transcription regulation, DNA- 2196 6164 factor IIF, binding, Nuclear protein, polypeptide 1, Phosphorylation, 3D-structure 74 kDa NM_002097 GTF3A general transcription Transcription regulation, Zinc-finger, 2197 6165 factor IIIA Metal-binding, DNA-binding, RNA- binding, Repeat, Nuclear protein, Polymorphism, Initiation factor NM_002103 GYS1 glycogen synthase 1 Glycogen biosynthesis, Transferase, 2198 6166 (muscle) Glycosyltransferase, Allosteric enzyme, Phosphorylation, Disease mutation, Diabetes mellitus, Polymorphism, Hypothetical protein NM_002104 GZMK granzyme K (serine Hydrolase, Serine protease, 2199 6167 protease, granzyme Zymogen, Signal, 3D-structure 3; tryptase II) NM_002105 H2AFX H2A histone family, Chromosomal protein, Nucleosome 2200 6168 member X core, Nuclear protein, DNA-binding, Multigene family, Acetylation NM_002107 H3F3A H3 histone, family Nuclear protein, Chromosomal 2201 6169 3A protein, DNA-binding, Nucleosome core, Multigene family NM_002108 HAL histidine ammonia- Lyase, Histidine metabolism, 2202 6170 lyase Polymorphism NM_002109 HARS histidyl-tRNA Aminoacyl-tRNA synthetase, Protein 2203 6171 synthetase biosynthesis, Ligase, ATP-binding, Hypothetical protein, Repeat, WD repeat NM_002110 HCK hemopoietic cell Transferase, Tyrosine-protein 2204 6172 kinase kinase, Phosphorylation, ATP- binding, Lipoprotein, Myristate, Palmitate, SH2 domain, SH3 domain, Alternative initiation, 3D- structure NM_002115 HK3 hexokinase 3 (white Kinase, Transferase, Glycolysis, 2205 6173 cell) Allosteric enzyme, Repeat, ATP- binding, Membrane NM_002131 HMGA1 high mobility group Nuclear protein, Chromosomal 2206 6174 AT-hook 1 protein, DNA-binding, Repeat, Transcription regulation, Alternative splicing, Phosphorylation, Acetylation, Chromosomal translocation, 3D-structure NM_002133 HMOX1 heme oxygenase Cyclin, Heme, Oxidoreductase, 2207 6175 (decycling) 1 Microsome, Multigene family, 3D- structure NM_002134 HMOX2 heme oxygenase Heme, Oxidoreductase, Microsome, 2208 6176 (decycling) 2 Multigene family, Repeat NM_002136 HNRPA1 heterogeneous Hypothetical protein, Nucleocapsid, 2209 6177 nuclear Ribonucleoprotein, Nuclear protein, ribonucleoprotein A1 RNA-binding, Repeat, Methylation, Alternative splicing, 3D-structure, Polymorphism NM_002139 RBMX RNA binding motif Hypothetical protein, Nuclear 2210 6178 protein, X-linked protein, RNA-binding, Ribonucleoprotein, Glycoprotein NM_002155 HSPA6 heat shock 70 kDa ATP-binding, Heat shock, Multigene 2211 6179 protein 6 (HSP70B′) family NM_002156 HSPD1 heat shock 60 kDa Chaperone, ATP-binding, 2212 6180 protein 1 Mitochondrion, Transit peptide (chaperonin) NM_002157 HSPE1 heat shock 10 kDa Chaperone, Mitochondrion, Heat 2213 6181 protein 1 shock, Acetylation (chaperonin 10) NM_002162 ICAM3 intercellular Immunoglobulin domain, Cell 2214 6182 adhesion molecule 3 adhesion, Glycoprotein, Transmembrane, Repeat, Signal, Phosphorylation NM_002180 IGHMBP2 immunoglobulin mu Hydrolase, Helicase, ATP-binding, 2215 6183 binding protein 2 DNA-binding, Nuclear protein, Transcription regulation, Activator, 3D-structure NM_002191 INHA inhibin, alpha Growth factor, Hormone, 2216 6184 Glycoprotein, Signal, Polymorphism NM_002194 INPP1 inositol Hydrolase, Lithium 2217 6185 polyphosphate-1- phosphatase NM_002205 ITGA5 integrin, alpha 5 Integrin, Cell adhesion, Receptor, 2218 6186 (fibronectin receptor, Glycoprotein, Transmembrane, alpha polypeptide) Signal, Calcium, Repeat NM_002209 ITGAL integrin, alpha L Integrin, Cell adhesion, Receptor, 2219 6187 (antigen CD11A Glycoprotein, Transmembrane, (p180), lymphocyte Signal, 3D-structure, Magnesium, function-associated Calcium, Repeat, Alternative antigen 1; alpha splicing, Hypothetical protein polypeptide) NM_002218 ITIH4 inter-alpha (globulin) Acute phase, Serine protease 2220 6188 inhibitor H4 (plasma inhibitor, Repeat, Signal, Multigene Kallikrein-sensitive family, Glycoprotein, Alternative glycoprotein) splicing, Polymorphism NM_002220 ITPKA inositol 1,4,5- Kinase, Transferase, Calmodulin- 2221 6189 trisphosphate 3- binding kinase A NM_002222 ITPR1 inositol 1,4,5- Receptor, Transmembrane, 2222 6190 triphosphate Phosphorylation, Endoplasmic receptor, type 1 reticulum, Ionic channel, Ion transport, Calcium channel, Alternative splicing, Repeat NM_002226 JAG2 jagged 2 Calcium-binding, EGF-like domain, 2223 6191 Glycoprotein, Developmental protein, Repeat, Signal, Transmembrane, Alternative splicing NM_002228 JUN v-jun sarcoma virus Proto-oncogene, Transcription 2224 6192 17 oncogene regulation, DNA-binding, 3D- homolog (avian) structure, Nuclear protein, Phosphorylation, Polymorphism NM_002236 KCNF1 potassium voltage- Transport, Ion transport, Ionic 2225 6193 gated channel, channel, Voltage-gated channel, subfamily F, member 1 Potassium channel, Potassium, Potassium transport, Transmembrane, Multigene family NM_002243 KCNJ15 potassium inwardly- Hypothetical protein, Ionic channel, 2226 6194 rectifying channel, Ion transport, Voltage-gated subfamily J, member channel, Transmembrane, 15 Potassium transport NM_002250 KCNN4 potassium Ionic channel, Transmembrane, Ion 2227 6195 intermediate/small transport, Calmodulin-binding conductance calcium-activated channel, subfamily N, member 4 NM_002258 KLRB1 killer cell lectin-like 2228 6196 receptor subfamily B, member 1 NM_002267 KPNA3 karyopherin alpha 3 Hypothetical protein, Transport, 2229 6197 (importin alpha 4) Protein transport, Repeat, Nuclear protein, Polymorphism NM_002271 KPNB3 karyopherin Hypothetical protein, Transport, 2230 6198 (importin) beta 3 Protein transport, Repeat, Nuclear protein, Polymorphism NM_002273 KRT8 keratin 8 Intermediate filament, Coiled coil, 2231 6199 Keratin, Phosphorylation NM_002275 KRT15 keratin 15 Intermediate filament, Coiled coil, 2232 6200 Keratin NM_002277 KRTHA1 keratin, hair, acidic, 1 Intermediate filament, Coiled coil, 2233 6201 Keratin NM_002278 KRTHA2 keratin, hair, acidic, 2 Intermediate filament, Coiled coil, 2234 6202 Keratin NM_002282 KRTHB3 keratin, hair, basic, 3 Coiled coil, Intermediate filament 2235 6203 NM_002296 LBR lamin B receptor Receptor, Transmembrane, 2236 6204 Phosphorylation, Nuclear protein, DNA-binding NM_002298 LCP1 lymphocyte cytosolic Calcium-binding, Phosphorylation, 2237 6205 protein 1 (L-plastin) Actin-binding, Repeat, Polymorphism NM_002299 LCT lactase Hydrolase, Glycosidase, Zymogen, 2238 6206 Signal, Transmembrane, Repeat NM_002300 LDHB lactate Oxidoreductase, NAD, Glycolysis, 2239 6207 dehydrogenase B Multigene family, Disease mutation, 3D-structure NM_002306 LGALS3 lectin, galactoside- Galectin, Lectin, IgE-binding protein, 2240 6208 binding, soluble, 3 Repeat, Phosphorylation, (galectin 3) Acetylation, Nuclear protein, Polymorphism, 3D-structure NM_002311 LIG3 ligase III, DNA, ATP- DNA repair, DNA replication, DNA 2241 6209 dependent recombination, Cell division, Ligase, ATP-binding, Zinc-finger, Nuclear protein, Alternative splicing, 3D- structure, Hypothetical protein NM_002313 ABLIM1 actin binding LIM LIM domain, Metal-binding, Zinc, 2242 6210 protein 1 Hypothetical protein NM_002316 LMX1B LIM homeobox DNA-binding, Homeobox, LIM 2243 6211 transcription factor 1, domain, Metal-binding, Nuclear beta protein, Zinc, Developmental protein, Repeat, Activator, Transcription regulation, Alternative splicing, Disease mutation NM_002332 LRP1 low density Receptor, Transmembrane, Repeat, 2244 6212 lipoprotein-related Endocytosis, Glycoprotein, Signal, protein 1 (alpha-2- Calcium-binding, EGF-like domain, macroglobulin Coated pits, 3D-structure, receptor) Polymorphism NM_002335 LRP5 low density Receptor, Lipoprotein 2245 6213 lipoprotein receptor- related protein 5 NM_002337 LRPAP1 low density Signal, Heparin-binding, 2246 6214 lipoprotein receptor- Glycoprotein, Antigen, 3D-structure, related protein Polymorphism associated protein 1 NM_002339 LSP1 lymphocyte-specific T-cell, Phosphorylation, 2247 6215 protein 1 Polymorphism NM_002341 LTB lymphotoxin beta Cytokine, Transmembrane, 2248 6216 (TNF superfamily, Glycoprotein, Signal-anchor, member 3) Alternative splicing, Polymorphism NM_002343 LTF lactotransferrin Glycoprotein, Iron transport, Metal- 2249 6217 binding, Transport, Repeat, Signal, Polymorphism, 3D-structure NM_002357 MAD MAX dimerization Nuclear protein, DNA-binding, 2250 6218 protein 1 Transcription regulation, Repressor, 3D-structure NM_002375 MAP4 microtubule- Hypothetical protein, Microtubule, 2251 6219 associated protein 4 Repeat, Phosphorylation, Alternative splicing NM_002382 MAX MAX protein Hypothetical protein, Transcription 2252 6220 regulation, Activator, Repressor, Nuclear protein, DNA-binding, Phosphorylation, Alternative splicing, 3D-structure NM_002394 SLC3A2 solute carrier family Glycoprotein, Transmembrane, 2253 6221 3 (activators of Signal-anchor dibasic and neutral amino acid transport), member 2 NM_002402 MEST mesoderm specific Aromatic hydrocarbons catabolism, 2254 6222 transcript homolog Detoxification, Hydrolase, (mouse) Hypothetical protein NM_002406 MGAT1 mannosyl (alpha- Transferase, Glycosyltransferase, 2255 6223 1,3-)-glycoprotein Transmembrane, Signal-anchor, beta-1,2-N- Golgi stack, Hypothetical protein acetylglucosaminyltransferase NM_002419 MAP3K11 mitogen-activated ATP-binding, Kinase, SH3 domain, 2256 6224 protein kinase Serine/threonine-protein kinase, kinase kinase 11 Transferase NM_002424 MMP8 matrix Hydrolase, Metalloprotease, 2257 6225 metalloproteinase 8 Glycoprotein, Calcium-binding, (neutrophil Metal-binding, Zinc, Zymogen, collagenase) Collagen degradation, Extracellular matrix, Signal, 3D-structure NM_002431 MNAT1 menage a trois 1 Transcription regulation, Cell cycle, 2258 6226 (CAK assembly Nuclear protein, Zinc-finger, 3D- factor) structure NM_002432 MNDA myeloid cell nuclear Interferon induction, Nuclear protein, 2259 6227 differentiation DNA-binding, Transcription antigen regulation, Activator, Repressor, Polymorphism NM_002435 MPI mannose phosphate Isomerase, Zinc, Disease mutation 2260 6228 isomerase NM_002442 MSI1 musashi homolog 1 RNA-binding 2261 6229 (Drosophila) NM_002453 MTIF2 mitochondrial Initiation factor, Protein biosynthesis, 2262 6230 translational initiation GTP-binding, Transit peptide, factor 2 Mitochondrion, Polymorphism NM_002455 MTX1 metaxin 1 Mitochondrion, Outer membrane, 2263 6231 Transmembrane, Transport, Protein transport NM_002475 MLC1SA myosin light chain 1 Myosin, Muscle protein, Multigene 2264 6232 slow a family NM_002483 CEACAM6 carcinoembryonic Immunoglobulin domain, Signal, 2265 6233 antigen-related cell Antigen, Glycoprotein, GPI-anchor, adhesion molecule 6 Repeat, Lipoprotein (non-specific cross reacting antigen) NM_002486 NCBP1 nuclear cap binding Transport, mRNA transport, Nuclear 2266 6234 protein subunit 1, protein, RNA-binding, 3D-structure 80 kDa NM_002492 NDUFB5 NADH Oxidoreductase, NAD, Ubiquinone, 2267 6235 dehydrogenase Mitochondrion, Transit peptide (ubiquinone) 1 beta subcomplex, 5, 16 kDa NM_002495 NDUFS4 NADH Oxidoreductase, NAD, Ubiquinone, 2268 6236 dehydrogenase Mitochondrion, Transit peptide, (ubiquinone) Fe—S Polymorphism protein 4, 18 kDa (NADH-coenzyme Q reductase) NM_002499 NEO1 neogenin homolog 1 Cell adhesion, Repeat, Signal, 2269 6237 (chicken) Transmembrane, Immunoglobulin domain, Glycoprotein, Alternative splicing NM_002512 NME2 non-metastatic cells Transferase, Kinase, ATP-binding, 2270 6238 2, protein (NM23B) Nuclear protein, Anti-oncogene expressed in DNA-binding, Transcription regulation, Activator, 3D-structure NM_002517 NPAS1 neuronal PAS Repeat, DNA-binding, Nuclear 2271 6239 domain protein 1 protein, Transcription regulation NM_002520 NPM1 nucleophosmin Hypothetical protein, Transcription 2272 6240 (nucleolar regulation, Nuclear protein, DNA- phosphoprotein B23, binding, Zinc-finger, Proto- numatrin) oncogene, Chromosomal translocation, Alternative splicing, Repeat, Coiled coil, 3D-structure, Metal-binding, Receptor, Multigene family, Phosphorylation, RNA- NM_002524 NRAS neuroblastoma RAS Hypothetical protein, RNA-binding, 2273 6241 viral (v-ras) Repeat, Alternative splicing, Proto- oncogene homolog oncogene, GTP-binding, Prenylation, Lipoprotein, Disease mutation NM_002528 NTHL1 nth endonuclease III- Hydrolase, Nuclease, Endonuclease, 2274 6242 like 1 (E. coli) Multifunctional enzyme, DNA repair, Glycosidase, Lyase, Iron-sulfur, 4Fe—4S, Nuclear protein, Polymorphism NM_002532 NUP88 nucleoporin 88 kDa Nuclear protein, Transport, Coiled 2275 6243 coil NM_002541 OGDH oxoglutarate (alpha- Glycolysis, Oxidoreductase, 2276 6244 ketoglutarate) Flavoprotein, Thiamine dehydrogenase pyrophosphate, Mitochondrion, (lipoamide) Transit peptide, Hypothetical protein NM_002543 OLR1 oxidised low density Lectin, Lipoprotein, Receptor 2277 6245 lipoprotein (lectin- like) receptor 1 NM_002553 ORC5L origin recognition DNA replication, Nuclear protein, 2278 6246 complex, subunit 5- ATP-binding, Polymorphism like (yeast) NM_002555 SLC22A1L solute carrier family Hypothetical protein 2279 6247 22 (organic cation transporter), member 1-like NM_002557 OVGP1 oviductal Glycoprotein, Fertilization, Signal, 2280 6248 glycoprotein 1, Polymorphism 120 kDa (mucin 9, oviductin) NM_002564 P2RY2 purinergic receptor G-protein coupled receptor, 2281 6249 P2Y, G-protein Transmembrane, Glycoprotein coupled, 2 NM_002573 PAFAH1B3 platelet-activating Hydrolase, Lipid degradation 2282 6250 factor acetylhydrolase, isoform lb, gamma subunit 29 kDa NM_002574 PRDX1 peroxiredoxin 1 Antioxidant, Peroxidase, 2283 6251 Oxidoreductase, Redox-active center NM_002576 PAK1 p21/Cdc42/Rac1- Apoptosis, Transferase, 2284 6252 activated kinase 1 Serine/threonine-protein kinase, (STE20 homolog, ATP-binding, Phosphorylation, 3D- yeast) structure, Kinase NM_002585 PBX1 pre-B-cell leukemia Transcription regulation, DNA- 2285 6253 transcription factor 1 binding, Nuclear protein, Activator, Repressor, Homeobox, Proto- oncogene, Chromosomal translocation, Alternative splicing, Steroidogenesis, Sexual differentiation, 3D-structure, Phosphorylation NM_002587 PCDH1 protocadherin 1 Cell adhesion, Transmembrane, 2286 6254 (cadherin-like 1) Calcium-binding, Repeat, Signal, Alternative splicing NM_002598 PDCD2 programmed cell Zinc-finger, DNA-binding, Nuclear 2287 6255 death 2 protein, Apoptosis NM_002601 PDE6D phosphodiesterase Hydrolase, cGMP, Vision, 3D- 2288 6256 6D, cGMP-specific, structure rod, delta NM_002608 PDGFB platelet-derived Mitogen, Growth factor, Proto- 2289 6257 growth factor beta oncogene, Platelet, Signal, polypeptide (simian Pharmaceutical, 3D-structure, sarcoma viral (v-sis) Polymorphism, Chromosomal oncogene homolog) translocation NM_002611 PDK2 pyruvate Kinase, Transferase, Transit peptide, 2290 6258 dehydrogenase Mitochondrion, Multigene family kinase, isoenzyme 2 NM_002613 PDPK1 3-phosphoinositide Transferase, Serine/threonine- 2291 6259 dependent protein protein kinase, ATP-binding, kinase-1 Phosphorylation, Membrane, Alternative splicing, Kinase NM_002616 PER1 period homolog 1 Transcription regulation, Nuclear 2292 6260 (Drosophila) protein, Repeat, Biological rhythms, Alternative splicing NM_002621 PFC properdin P factor, Signal, Complement alternate 2293 6261 complement pathway, Glycoprotein, Repeat, Disease mutation NM_002629 PGAM1 phosphoglycerate Isomerase, Hydrolase, Glycolysis, 2294 6262 mutase 1 (brain) Acetylation, 3D-structure NM_002631 PGD phosphogluconate Oxidoreductase, Pentose shunt, 2295 6263 dehydrogenase NADP NM_002633 PGM1 phosphoglucomutase 1 Isomerase, Phosphorylation, 2296 6264 Magnesium, Polymorphism, Alternative splicing, Hypothetical protein NM_002635 SLC25A3 solute carrier family Mitochondrion, Inner membrane, 2297 6265 25 (mitochondrial Repeat, Transit peptide, carrier; phosphate Transmembrane, Transport, carrier), member 3 Symport, Alternative splicing, Hypothetical protein NM_002640 SERPINB8 serine (or cysteine) Protease inhibitor, Serine protease 2298 6266 proteinase inhibitor, inhibitor, Serpin clade B (ovalbumin), member 8 NM_002649 PIK3CG phosphoinositide-3- Kinase, Transferase, Multigene 2299 6267 kinase, catalytic, family, 3D-structure gamma polypeptide NM_002650 PIK4CA phosphatidylinositol Transferase, Kinase, Alternative 2300 6268 4-kinase, catalytic, splicing alpha polypeptide NM_002651 PIK4CB phosphatidylinositol Transferase, Kinase, Golgi stack, 2301 6269 4-kinase, catalytic, Phosphorylation, Alternative splicing beta polypeptide NM_002653 PITX1 paired-like Homeobox, DNA-binding, 2302 6270 homeodomain Developmental protein, Nuclear transcription factor 1 protein, Transcription regulation, Activator NM_002654 PKM2 pyruvate kinase, Transferase, Kinase, Glycolysis, 2303 6271 muscle Multigene family, Magnesium, Alternative splicing, Hypothetical protein NM_002655 PLAG1 pleiomorphic Metal-binding, Zinc, Zinc-finger 2304 6272 adenoma gene 1 NM_002659 PLAUR plasminogen Receptor, Signal, Glycoprotein, GPI- 2305 6273 activator, urokinase anchor, Repeat, Alternative splicing, receptor Polymorphism, Lipoprotein, Kinase NM_002661 PLCG2 phospholipase C, Hydrolase, Lipid degradation, 2306 6274 gamma 2 Transducer, SH2 domain, SH3 (phosphatidylinositol domain, Repeat, Calcium-binding, specific) Phosphorylation NM_002668 PLP2 proteolipid protein 2 Transmembrane, Glycoprotein, 2307 6275 (colonic epithelium- Polymorphism enriched) NM_002676 PMM1 phosphomannomutase 1 Isomerase 2308 6276 NM_002685 PMSCL2 polymyositis/scleroderma Hydrolase, Nuclease, Exonuclease, 2309 6277 autoantigen 2, rRNA processing, Nuclear protein, 100 kDa RNA-binding, Antigen, Alternative splicing, Hypothetical protein NM_002686 PNMT phenylethanolamine Transferase, Methyltransferase, 2310 6278 N-methyltransferase Catecholamine biosynthesis, 3D- structure NM_002688 PNUTL1 peanut-like 1 Hypothetical protein, Cell division, 2311 6279 (Drosophila) GTP-binding, Coiled coil, Platelet, Transmembrane, Glycoprotein, Hemostasis, Blood coagulation, Signal, Phosphorylation, Cell adhesion, Leucine-rich repeat NM_002691 POLD1 polymerase (DNA DNA replication, DNA-binding, DNA- 2312 6280 directed), delta 1, directed DNA polymerase, catalytic subunit Transferase, Hydrolase, 125 kDa Exonuclease, Zinc-finger, Nuclear protein, Polymorphism NM_002692 POLE2 polymerase (DNA Transferase, DNA-directed DNA 2313 6281 directed), epsilon 2 polymerase, DNA replication, DNA- (p59 subunit) binding, Nuclear protein NM_002710 PPP1CC protein phosphatase Hydrolase, Metal-binding, Iron, 2314 6282 1, catalytic subunit, Manganese, Glycogen metabolism, gamma isoform Multigene family, Cell division, Alternative splicing, 3D-structure NM_002720 PPP4C protein phosphatase Hydrolase, Metal-binding, Iron, 2315 6283 4 (formerly X), Manganese catalytic subunit NM_002727 PRG1 proteoglycan 1, Glycoprotein, Proteoglycan, Repeat, 2316 6284 secretory granule Signal NM_002728 PRG2 proteoglycan 2, bone Eosinophil, Signal, Immune 2317 6285 marrow (natural killer response, Antibiotic, Lectin, cell activator, Proteoglycan, Glycoprotein, Heparin- eosinophil granule binding, 3D-structure major basic protein) NM_002731 PRKACB protein kinase, ATP-binding, Kinase, 2318 6286 cAMP-dependent, Serine/threonine-protein kinase, catalytic, beta Transferase, Nuclear protein, cAMP, Myristate, Phosphorylation, Multigene family, Lipoprotein NM_002733 PRKAG1 protein kinase, AMP- Fatty acid biosynthesis, Repeat, 2319 6287 activated, gamma 1 CBS domain, Hypothetical protein non-catalytic subunit NM_002738 PRKCB1 protein kinase C, Transferase, Serine/threonine- 2320 6288 beta 1 protein kinase, Membrane, ATP- binding, Calcium-binding, Metal- binding, Zinc, Repeat, Phorbol-ester binding, Phosphorylation, Alternative splicing NM_002741 PRKCL1 protein kinase C-like 1 Transferase, ATP-binding, 2321 6289 Serine/threonine-protein kinase, Phosphorylation, Polymorphism, 3D- structure NM_002745 MAPK1 mitogen-activated Transferase, Serine/threonine- 2322 6290 protein kinase 1 protein kinase, ATP-binding, Cell cycle, Phosphorylation, 3D-structure NM_002748 MAPK6 mitogen-activated Kinase, Transferase, 2323 6291 protein kinase 6 Serine/threonine-protein kinase, ATP-binding, Cell cycle NM_002749 MAPK7 mitogen-activated ATP-binding, Kinase, 2324 6292 protein kinase 7 Serine/threonine-protein kinase, Transferase, Cell cycle, Phosphorylation, Cell adhesion, Extracellular matrix, Glycoprotein, Calcium, Signal NM_002756 MAP2K3 mitogen-activated Transferase, Serine/threonine- 2325 6293 protein kinase protein kinase, Tyrosine-protein kinase 3 kinase, ATP-binding, Phosphorylation, Alternative splicing, Disease mutation NM_002757 MAP2K5 mitogen-activated ATP-binding, Kinase, 2326 6294 protein kinase Serine/threonine-protein kinase, kinase 5 Transferase NM_002758 MAP2K6 mitogen-activated Transferase, Serine/threonine- 2327 6295 protein kinase protein kinase, Tyrosine-protein kinase 6 kinase, ATP-binding, Phosphorylation, Alternative splicing NM_002764 PRPS1 phosphoribosyl Nucleotide biosynthesis, 2328 6296 pyrophosphate Transferase, Kinase, Magnesium, synthetase 1 Multigene family, Gout, Disease mutation NM_002765 PRPS2 phosphoribosyl Nucleotide biosynthesis, 2329 6297 pyrophosphate Transferase, Kinase, Magnesium, synthetase 2 Multigene family NM_002767 PRPSAP2 phosphoribosyl Nucleotide biosynthesis 2330 6298 pyrophosphate synthetase- associated protein 2 NM_002770 PRSS2 protease, serine, 2 Hydrolase, Protease, Serine 2331 6299 (trypsin 2) protease, Digestion, Pancreas, Zymogen, Calcium-binding, Signal, Multigene family NM_002777 PRTN3 proteinase 3 (serine Collagen degradation, Hydrolase, 2332 6300 proteinase, Serine protease, Signal, Zymogen, neutrophil, Wegener Glycoprotein, Polymorphism, 3D- granulomatosis structure autoantigen) NM_002782 PSG6 pregnancy specific Immunoglobulin domain, 2333 6301 beta-1-glycoprotein 6 Glycoprotein, Signal, Multigene family, Repeat, Polymorphism, Alternative splicing, Hypothetical protein, Flavoprotein, Lyase, Thiamine pyrophosphate NM_002786 PSMA1 proteasome Proteasome, Hydrolase, Protease, 2334 6302 (prosome, Acetylation, Alternative splicing, macropain) subunit, Threonine protease alpha type, 1 NM_002788 PSMA3 proteasome Proteasome, Hydrolase, Protease, 2335 6303 (prosome, Acetylation, Alternative splicing, macropain) subunit, Phosphorylation, Threonine protease alpha type, 3 NM_002790 PSMA5 proteasome Proteasome, Hydrolase, Protease, 2336 6304 (prosome, Threonine protease macropain) subunit, alpha type, 5 NM_002793 PSMB1 proteasome Proteasome, Hydrolase, Protease, 2337 6305 (prosome, Threonine protease macropain) subunit, beta type, 1 NM_002794 PSMB2 proteasome Proteasome, Hydrolase, Protease, 2338 6306 (prosome, Threonine protease macropain) subunit, beta type, 2 NM_002796 PSMB4 proteasome Proteasome, Hydrolase, Protease, 2339 6307 (prosome, Zymogen, Polymorphism, Threonine macropain) subunit, protease beta type, 4 NM_002805 PSMC5 proteasome ATP-binding, Proteasome 2340 6308 (prosome, macropain) 26S subunit, ATPase, 5 NM_002807 PSMD1 proteasome Proteasome, Repeat 2341 6309 (prosome, macropain) 26S subunit, non- ATPase, 1 NM_002809 PSMD3 proteasome Hypothetical protein, Proteasome 2342 6310 (prosome, macropain) 26S subunit, non- ATPase, 3 NM_002815 PSMD11 proteasome Proteasome 2343 6311 (prosome, macropain) 26S subunit, non- ATPase, 11 NM_002818 PSME2 proteasome Proteasome, Interferon induction 2344 6312 (prosome, macropain) activator subunit 2 (PA28 beta) NM_002821 PTK7 PTK7 protein ATP-binding, Immunoglobulin 2345 6313 tyrosine kinase 7 domain, Receptor, Transferase, Transmembrane, Signal, Glycoprotein, Cell adhesion, Repeat, Hypothetical protein, Kinase, Tyrosine-protein kinase NM_002824 PTMS parathymosin Hypothetical protein, Immune 2346 6314 response, Acetylation NM_002826 QSCN6 quiescin Q6 Redox-active center 2347 6315 NM_002831 PTPN6 protein tyrosine Hydrolase, SH2 domain, Repeat, 2348 6316 phosphatase, non- Phosphorylation, Alternative splicing, receptor type 6 3D-structure NM_002842 PTPRH protein tyrosine Signal 2349 6317 phosphatase, receptor type, H NM_002843 PTPRJ protein tyrosine Signal, Glycoprotein, 2350 6318 phosphatase, Transmembrane, Repeat, receptor type, J Hydrolase, Disease mutation, Receptor NM_002850 PTPRS protein tyrosine Hydrolase, Receptor, Glycoprotein, 2351 6319 phosphatase, Signal, Transmembrane, Cell receptor type, S adhesion, Immunoglobulin domain, Alternative splicing, Repeat NM_002852 PTX3 pentaxin-related Pentaxin, Glycoprotein, Signal 2352 6320 gene, rapidly induced by IL-1 beta NM_002859 PXN hypothetical protein Cytoskeleton, Phosphorylation, LIM 2353 6321 FLJ23042 domain, Repeat, Metal-binding, Zinc, Alternative splicing, 3D-structure, Hypothetical protein NM_002862 PYGB phosphorylase, Carbohydrate metabolism, 2354 6322 glycogen; brain Glycosyltransferase, Pyridoxal phosphate, Transferase, Glycogen metabolism, Allosteric enzyme, Phosphorylation NM_002863 PYGL phosphorylase, Transferase, Glycosyltransferase, 2355 6323 glycogen; liver (Hers Carbohydrate metabolism, Glycogen disease, glycogen metabolism, Allosteric enzyme, storage disease type Pyridoxal phosphate, VI) Phosphorylation, Glycogen storage disease, Disease mutation, Polymorphism, 3D-structure NM_002865 RAB2 RAB2, member RAS GTP-binding, Transport, Protein 2356 6324 oncogene family transport, Endoplasmic reticulum, Golgi stack, Lipoprotein, Prenylation NM_002872 RAC2 ras-related C3 GTP-binding, Prenylation, 2357 6325 botulinum toxin Lipoprotein, 3D-structure substrate 2 (rho family, small GTP binding protein Rac2) NM_002878 RAD51L3 RAD51-like 3 (S. cerevisiae) DNA damage, DNA repair, DNA 2358 6326 recombination, DNA-binding, ATP- binding, Nuclear protein, Alternative splicing, Hypothetical protein NM_002880 RAF1 v-raf-1 murine Hypothetical protein, Metal-binding, 2359 6327 leukemia viral Zinc, Zinc-finger, Transferase, oncogene homolog 1 Serine/threonine-protein kinase, Proto-oncogene, ATP-binding, Phorbol-ester binding, Phosphorylation, 3D-structure, Repeat NM_002881 RALB v-ral simian GTP-binding, Prenylation, 2360 6328 leukemia viral Lipoprotein oncogene homolog B (ras related; GTP binding protein) NM_002883 RANGAP1 Ran GTPase Hypothetical protein, GTPase 2361 6329 activating protein 1 activation, Repeat, Leucine-rich repeat, Ubl conjugation NM_002887 RARS arginyl-tRNA Aminoacyl-tRNA synthetase, Protein 2362 6330 synthetase biosynthesis, Ligase, ATP-binding, Alternative initiation NM_002893 RBBP7 retinoblastoma Nuclear protein, Repeat, WD repeat 2363 6331 binding protein 7 NM_002896 RBM4 RNA binding motif Zinc-finger 2364 6332 protein 4 NM_002897 RBMS1 RNA binding motif, DNA-binding, DNA replication, RNA- 2365 6333 single stranded binding, Nuclear protein, interacting protein 1 Phosphorylation NM_002901 RCN1 reticulocalbin 1, EF- Calcium-binding, Endoplasmic 2366 6334 hand calcium reticulum, Signal, Glycoprotein, binding domain Repeat, Polymorphism NM_002902 RCN2 reticulocalbin 2, EF- Calcium-binding, Endoplasmic 2367 6335 hand calcium reticulum, Signal, Repeat binding domain NM_002903 RCV1 recoverin Calcium-binding, Repeat, Myristate, 2368 6336 Vision, Lipoprotein NM_002905 RDH5 retinol Oxidoreductase, NAD, Membrane, 2369 6337 dehydrogenase 5 Vision, Disease mutation, (11-cis and 9-cis) Polymorphism NM_002910 RENBP renin binding protein Isomerase 2370 6338 NM_002918 RFX1 regulatory factor X, 1 DNA-binding, Transcription 2371 6339 (influences HLA regulation, Activator, Nuclear class II expression) protein, 3D-structure NM_002922 RGS1 regulator of G- Signal transduction inhibitor, B-cell 2372 6340 protein signalling 1 activation, Phosphorylation NM_002923 RGS2 regulator of G- Signal transduction inhibitor, Cell 2373 6341 protein signalling 2, cycle, Phosphorylation 24 kDa NM_002934 RNASE2 ribonuclease, RNase Hydrolase, Nuclease, Endonuclease, 2374 6342 A family, 2 (liver, Chemotaxis, Eosinophil, eosinophil-derived Glycoprotein, Signal, Polymorphism, neurotoxin) 3D-structure NM_002935 RNASE3 ribonuclease, RNase Hydrolase, Nuclease, Endonuclease, 2375 6343 A family, 3 Eosinophil, Glycoprotein, Antibiotic, (eosinophil cationic Signal, Polymorphism, 3D-structure protein) NM_002936 RNASEH1 ribonuclease H1 Hydrolase, Nuclease, Endonuclease, 2376 6344 Magnesium NM_002939 RNH ribonuclease/angiogenin Repeat, Leucine-rich repeat, 3D- 2377 6345 inhibitor structure, Polymorphism, Hypothetical protein NM_002940 ABCE1 ATP-binding Capsid assembly, Chaperone, 2378 6346 cassette, sub-family Mitochondrion, ATP-binding, Repeat E (OABP), member 1 NM_002953 RPS6KA1 ribosomal protein S6 Transferase, Serine/threonine- 2379 6347 kinase, 90 kDa, protein kinase, ATP-binding, Repeat, polypeptide 1 Multigene family NM_002957 RXRA retinoid X receptor, Receptor, Transcription regulation, 2380 6348 alpha DNA-binding, Nuclear protein, Zinc- finger, Multigene family, 3D- structure, Polymorphism NM_002961 S100A4 S100 calcium Calcium-binding, 3D-structure 2381 6349 binding protein A4 (calcium protein, calvasculin, metastasin, murine placental homolog) NM_002964 S100A8 S100 calcium Macrophage, Calcium-binding, 3D- 2382 6350 binding protein A8 structure (calgranulin A) NM_002965 S100A9 S100 calcium Calcium-binding, Macrophage, 2383 6351 binding protein A9 Phosphorylation, Polymorphism, 3D- (calgranulin B) structure NM_002967 SAFB scaffold attachment Transcription regulation, Repressor, 2384 6352 factor B Nuclear protein, DNA-binding, RNA- binding, Phosphorylation NM_002969 MAPK12 mitogen-activated Transferase, Serine/threonine- 2385 6353 protein kinase 12 protein kinase, ATP-binding, Cell cycle, Phosphorylation, Polymorphism, 3D-structure NM_002978 SCNN1D sodium channel, Ion transport, Sodium transport, 2386 6354 nonvoltage-gated 1, Ionic channel, Transmembrane, delta Glycoprotein, Alternative splicing, Sodium channel NM_002984 CCL4 chemokine (C—C Cytokine, Chemotaxis, Inflammatory 2387 6355 motif) ligand 4 response, Signal, 3D-structure NM_002985 CCL5 chemokine (C—C Cytokine, Chemotaxis, T-cell, Signal, 2388 6356 motif) ligand 5 Inflammatory response, 3D-structure NM_003003 SEC14L1 SEC14-like 1 (S. cerevisiae) 2389 6357 NM_003006 SELPLG selectin P ligand Hypothetical protein, Cell adhesion, 2390 6358 Glycoprotein, Transmembrane, Signal, Repeat, Polymorphism, Sulfation, 3D-structure, Lectin, Selectin NM_003011 SET SET translocation Proto-oncogene, Chromosomal 2391 6359 (myeloid leukemia- translocation, Nuclear protein, associated) Phosphorylation NM_003021 SGT small glutamine-rich Chaperone, Repeat, TPR repeat, 2392 6360 tetratricopeptide Hypothetical protein repeat (TPR)- containing, alpha NM_003040 SLC4A2 solute carrier family Transmembrane, Glycoprotein, 2393 6361 4, anion exchanger, Transport, Antiport, Ion transport, member 2 Anion exchange, Lipoprotein, (erythrocyte Palmitate, Alternative splicing membrane protein band 3-like 1) NM_003044 SLC6A12 solute carrier family Neurotransmitter transport, 2394 6362 6 (neurotransmitter Transport, Transmembrane, transporter, Glycoprotein, Symport betaine/GABA), member 12 NM_003055 SLC18A3 choline Transport, Neurotransmitter 2395 6363 acetyltransferase transport, Transmembrane, Glycoprotein NM_003056 SLC19A1 solute carrier family Folate-binding, Transport, 2396 6364 19 (folate Transmembrane, Glycoprotein transporter), member 1 NM_003057 SLC22A1 solute carrier family Transmembrane 2397 6365 22 (organic cation transporter), member 1 NM_003059 SLC22A4 solute carrier family Transmembrane 2398 6366 22 (organic cation transporter), member 4 NM_003064 SLPI secretory leukocyte Serine protease inhibitor, Repeat, 2399 6367 protease inhibitor Signal (antileukoproteinase) NM_003066 SLPI secretory leukocyte Serine protease inhibitor, Repeat, 2400 6368 protease inhibitor Signal (antileukoproteinase) NM_003071 SMARCA3 SWI/SNF related, ATP-binding, DNA-binding, Helicase, 2401 6369 matrix associated, Hydrolase, Metal-binding, Zinc, Zinc- actin dependent finger regulator of chromatin, subfamily a, member 3 NM_003073 SMARCB1 SWI/SNF related, Hypothetical protein, Transcription 2402 6370 matrix associated, regulation, Activator, Nuclear actin dependent protein, Alternative splicing, Anti- regulator of oncogene chromatin, subfamily b, member 1 NM_003074 SMARCC1 SWI/SNF related, DNA-binding, Nuclear protein 2403 6371 matrix associated, actin dependent regulator of chromatin, subfamily c, member 1 NM_003077 SMARCD2 SWI/SNF related, 2404 6372 matrix associated, actin dependent regulator of chromatin, subfamily d, member 2 NM_003079 SMARCE1 SWI/SNE related, 2405 6373 matrix associated, actin dependent regulator of chromatin, subfamily e, member 1 NM_003084 SNAPC3 small nuclear RNA Hypothetical protein, Transcription 2406 6374 activating complex, regulation, DNA-binding polypeptide 3, 50 kDa NM_003085 SNCB synuclein, beta Phosphorylation, Repeat 2407 6375 NM_003086 SNAPC4 small nuclear RNA DNA-binding, Nuclear protein, 2408 6376 activating complex, Hypothetical protein polypeptide 4, 190 kDa NM_003088 FSCN1 fascin homolog 1, Actin-binding, Acetylation, 2409 6377 actin-bundling Phosphorylation, 3D-structure, protein Hypothetical protein (Strongylocentrotus purpuratus) NM_003090 SNRPA1 small nuclear Nuclear protein, RNA-binding, 2410 6378 ribonucleoprotein Ribonucleoprotein, Leucine-rich polypeptide A′ repeat, Repeat, 3D-structure NM_003092 SNRPB2 small nuclear mRNA processing, mRNA splicing, 2411 6379 ribonucleoprotein Nuclear protein, RNA-binding, polypeptide B″ Ribonucleoprotein, Repeat, Systemic lupus erythematosus, 3D- structure NM_003093 SNRPC small nuclear Nuclear protein, RNA-binding, 2412 6380 ribonucleoprotein Ribonucleoprotein, Zinc-finger polypeptide C NM_003094 SNRPE small nuclear Nuclear protein, Ribonucleoprotein, 2413 6381 ribonucleoprotein Systemic lupus erythematosus, polypeptide E mRNA splicing, mRNA processing, RNA-binding NM_003100 SNX2 sorting nexin 2 Transport, Protein transport 2414 6382 NM_003104 SORD sorbitol Oxidoreductase, Zinc, Metal-binding, 2415 6383 dehydrogenase NAD, Acetylation, Polymorphism NM_003105 SORL1 sortilin-related Endocytosis, Receptor, 2416 6384 receptor, L(DLR Transmembrane, EGF-like domain, class) A repeats- Repeat, Glycoprotein, LDL, Lipid containing transport, Cholesterol metabolism, Signal NM_003107 SOX4 SRY (sex DNA-binding, Nuclear protein, 2417 6385 determining region Transcription regulation, Activator Y)-box 4 NM_003120 SPI1 spleen focus forming Proto-oncogene, DNA-binding, 2418 6386 virus (SFFV) proviral Transcription regulation, Activator, integration oncogene Nuclear protein spi1 NM_003135 SRP19 signal recognition Signal recognition particle, RNA- 2419 6387 particle 19 kDa binding, Ribonucleoprotein, 3D- structure NM_003141 SSA1 Sjogren syndrome Systemic lupus erythematosus, Zinc- 2420 6388 antigen A1 (52 kDa, finger, Antigen, RNA-binding, ribonucleoprotein Ribonucleoprotein, DNA-binding, autoantigen SS- Polymorphism A/Ro) NM_003143 SSBP1 single-stranded DNA DNA-binding, DNA replication, 2421 6389 binding protein 1 Mitochondrion, Transit peptide, 3D- structure NM_003146 SSRP1 structure specific DNA-binding, Nuclear protein 2422 6390 recognition protein 1 NM_003150 STAT3 signal transducer Hypothetical protein, Transcription 2423 6391 and activator of regulation, Activator, DNA-binding, transcription 3 Nuclear protein, Phosphorylation, (acute-phase SH2 domain response factor) NM_003153 STAT6 signal transducer Transcription regulation, Repressor, 2424 6392 and activator of Alternative splicing, Activator, DNA- transcription 6, binding, Nuclear protein, interleukin-4 induced Phosphorylation, SH2 domain, Polymorphism NM_003163 STX1B1 Human mRNA for Neurotransmitter transport, Coiled 2425 6393 SYNTAXIN1B, coil, Transmembrane complete cds. NM_003168 SUPT4H1 suppressor of Ty 4 Nuclear protein, Transcription, Zinc- 2426 6394 homolog 1 (S. cerevisiae) finger NM_003169 SUPT5H suppressor of Ty 5 2427 6395 homolog (S. cerevisiae) NM_003171 SUPV3L1 suppressor of var1, ATP-binding, Helicase, Hydrolase 2428 6396 3-like 1 (S. cerevisiae) NM_003174 SVIL supervillin 2429 6397 NM_003177 SYK spleen tyrosine Transferase, Tyrosine-protein 2430 6398 kinase kinase, ATP-binding, Phosphorylation, SH2 domain, Repeat, Alternative splicing, 3D- structure NM_003190 TAPBP TAP binding protein Immunoglobulin domain, Signal, 2431 6399 (tapasin) Transmembrane, Endoplasmic reticulum, Microsome, Alternative splicing, Polymorphism NM_003191 TARS hypothetical protein Aminoacyl-tRNA synthetase, Protein 2432 6400 MGC9344 biosynthesis, Ligase, ATP-binding NM_003193 TBCE tubulin-specific 2433 6401 chaperone e NM_003197 TCEB1L S-phase kinase- Ubl conjugation pathway, Alternative 2434 6402 associated protein splicing, 3D-structure 1A (p19A) NM_003199 TCF4 transcription factor 4 Transcription regulation, DNA- 2435 6403 binding, Activator, Nuclear protein, Alternative splicing NM_003201 TFAM transcription factor Transcription regulation, DNA- 2436 6404 A, mitochondrial binding, Activator, Mitochondrion, Transit peptide, Repeat, Polymorphism NM_003202 TCF7 transcription factor 7 Transcription regulation, Activator, 2437 6405 (T-cell specific, Repressor, Trans-acting factor, HMG-box) Nuclear protein, DNA-binding, Wnt signaling pathway, Alternative splicing, Alternative promoter usage NM_003203 C2orf3 chromosome 2 open 2438 6406 reading frame 3 NM_003205 TCF12 transcription factor Transcription regulation, DNA- 2439 6407 12 (HTF4, helix- binding, Nuclear protein, loop-helix Developmental protein transcription factors 4) NM_003217 TEGT testis enhanced Apoptosis, Transmembrane 2440 6408 gene transcript (BAX inhibitor 1) NM_003226 TFF3 trefoil factor 3 Signal, 3D-structure 2441 6409 (intestinal) NM_003227 TFR2 transferrin receptor 2 Transmembrane, Glycoprotein, 2442 6410 Receptor, Signal-anchor, Alternative splicing, Disease mutation NM_003236 TGFA transforming growth EGF-like domain, Growth factor, 2443 6411 factor, alpha Mitogen, Glycoprotein, Transmembrane, Signal, 3D- structure, Lipoprotein, Palmitate NM_003245 TGM3 transglutaminase 3 Transferase, Acyltransferase, 2444 6412 (E polypeptide, Calcium-binding, Zymogen, protein-glutamine- Keratinization, 3D-structure gamma- glutamyltransferase) NM_003248 THBS4 thrombospondin 4 Glycoprotein, Cell adhesion, 2445 6413 Calcium-binding, Repeat, EGF like domain, Signal NM_003252 TIAL1 TIA1 cytotoxic RNA-binding, Apoptosis, Repeat 2446 6414 granule-associated RNA binding protein- like 1 NM_003255 TIMP2 tissue inhibitor of Hypothetical protein, 2447 6415 metalloproteinase 2 Metalloprotease inhibitor, Signal, 3D- structure NM_003263 TLR1 toll-like receptor 1 Receptor, Immune response, 2448 6416 Inflammatory response, Signal, Transmembrane, Repeat, Leucine- rich repeat, Glycoprotein, 3D- structure NM_003274 TMEM1 transmembrane Transport, Endoplasmic reticulum, 2449 6417 protein 1 Golgi stack, Polymorphism NM_003281 TNNI1 troponin I, skeletal, Muscle protein, Actin-binding, Ubl 2450 6418 slow conjugation pathway, Hydrolase, Thiol protease, Multigene family NM_003288 TPD52L2 tumor protein D52- Coiled coil, Alternative splicing 2451 6419 like 2 NM_003289 TPM2 tropomyosin 2 (beta) Muscle protein, Cytoskeleton, Actin- 2452 6420 binding, Coiled coil, Alternative splicing, Multigene family, Acetylation, Disease mutation NM_003290 TPM4 tropomyosin 4 Muscle protein, Cytoskeleton, Actin- 2453 6421 binding, Coiled coil, Alternative splicing, Multigene family NM_003299 TRA1 tumor rejection Chaperone, Endoplasmic reticulum, 2454 6422 antigen (gp96) 1 Glycoprotein, Calcium-binding, Signal NM_003307 TRPM2 Homo sapiens Ionic channel, Transmembrane, Ion 2455 6423 transient receptor transport, Calcium channel, potential cation Alternative splicing channel, subfamily M, member 2 (TRPM2), mRNA. NM_003310 TSSC1 tumor suppressing Repeat, WD repeat 2456 6424 subtransferable candidate 1 NM_003316 TTC3 tetratricopeptide Metal-binding, Zinc, Zinc-finger, 2457 6425 repeat domain 3 Repeat, TPR repeat, Alternative splicing, Polymorphism NM_003326 TNFSF4 tumor necrosis factor Cytokine, Transmembrane, 2458 6426 (ligand) superfamily, Glycoprotein, Signal-anchor member 4 (tax- transcriptionally activated glycoprotein 1, 34 kDa) NM_003329 TXN thioredoxin Redox-active center, Electron 2459 6427 transport, 3D-structure NM_003330 TXNRD1 thioredoxin Redox-active center, 2460 6428 reductase 1 Oxidoreductase, NADP, Flavoprotein, FAD NM_003331 TYK2 tyrosine kinase 2 Transferase, Tyrosine-protein 2461 6429 kinase, ATP-binding, Phosphorylation, SH2 domain, Repeat NM_003332 TYROBP TYRO protein Transmembrane, Signal, 2462 6430 tyrosine kinase Phosphorylation, Polymorphism, binding protein Receptor NM_003338 UBE2D1 ubiquitin-conjugating Ubl conjugation pathway, Ligase, 2463 6431 enzyme E2D 1 Multigene family (UBC4/5 homolog, yeast) NM_003341 UBE2E1 ubiquitin-conjugating Ubl conjugation pathway, Ligase, 2464 6432 enzyme E2E 1 Multigene family (UBC4/5 homolog, yeast) NM_003343 UBE2G2 ubiquitin-conjugating Ubl conjugation pathway, Ligase, 2465 6433 enzyme E2G 2 Multigene family, Hypothetical (UBC7 homolog, protein yeast) NM_003348 UBE2N ubiquitin-conjugating Ubl conjugation pathway, Ligase, 2466 6434 enzyme E2N Multigene family, 3D-structure (UBC13 homolog, yeast) NM_003358 UCP2 uncoupling protein 2 Mitochondrion, Inner membrane, 2467 6435 (mitochondrial, Repeat, Transmembrane, Transport, proton carrier) Polymorphism NM_003355 UGCG UDP-glucose Transferase, Glycosyltransferase, 2468 6436 ceramide Transmembrane, Signal-anchor, glucosyltransferase Endoplasmic reticulum NM_003362 UNG uracil-DNA DNA repair, Hydrolase, Glycosidase, 2469 6437 glycosylase Nuclear protein, Mitochondrion, Transit peptide, Disease mutation, Alternative splicing, 3D-structure NM_003364 UP uridine Transferase, Glycosyltransferase, 2470 6438 phosphorylase 1 Alternative splicing NM_003366 UQCRC2 ubiquinol- Mitochondrion, Inner membrane, 2471 6439 cytochrome c Electron transport, Respiratory reductase core chain, Oxidoreductase, Transit protein II peptide NM_003370 VASP vasodilator- Phosphorylation, Actin-binding, 3D- 2472 6440 stimulated structure phosphoprotein NM_003374 VDAC1 voltage-dependent Outer membrane, Porin, 2473 6441 anion channel 1 Mitochondrion, Acetylation NM_003375 VDAC2 voltage-dependent Outer membrane, Porin, 2474 6442 anion channel 2 Mitochondrion, Alternative splicing, Polymorphism NM_003377 VEGFB vascular endothelial Mitogen, Growth factor, 2475 6443 growth factor B Glycoprotein, Signal, Heparin- binding, Alternative splicing, Multigene family NM_003387 WASPIP Wiskott-Aldrich Actin-binding, Repeat, 2476 6444 syndrome protein Polymorphism interacting protein NM_003389 CORO2A coronin, actin Actin-binding, Repeat, WD repeat, 2477 6445 binding protein, 2A Coiled coil NM_003403 YY1 YY1 transcription Transcription regulation, Repressor, 2478 6446 factor Activator, Nuclear protein, Zinc- finger, Metal-binding, DNA-binding, Repeat, 3D-structure NM_003407 ZFP36 zinc finger protein Nuclear protein, Repeat, Metal- 2479 6447 36, C3H type, binding, Zinc-finger, DNA-binding homolog (mouse) NM_003426 ZNF74 zinc finger protein 74 Transcription regulation, DNA- 2480 6448 (Cos52) binding, RNA-binding, Zinc-finger, Metal-binding, Nuclear protein, Repeat, Alternative splicing, Polymorphism NM_003451 ZNF177 zinc finger protein Transcription regulation, DNA- 2481 6449 177 binding, Zinc-finger, Metal-binding, Nuclear protein, Repeat, Hypothetical protein NM_003457 ZNF207 zinc finger protein Zinc-finger, Metal-binding, DNA- 2482 6450 207 binding, Nuclear protein, Alternative splicing, Hypothetical protein NM_003461 ZYX zyxin LIM domain, Metal-binding, Zinc, 2483 6451 Repeat, Cell adhesion, Receptor NM_003465 CHIT1 chitinase 1 Carbohydrate metabolism, Chitin 2484 6452 (chitotriosidase) degradation, Polysaccharide degradation, Hydrolase, Glycosidase, Chitin-binding, Signal, Alternative splicing, 3D-structure NM_003466 PAX8 paired box gene 8 DNA-binding, Developmental 2485 6453 protein, Nuclear protein, Paired box, Transcription, Transcription regulation, Differentiation, Alternative splicing, Disease mutation, Polymorphism NM_003467 CXCR4 chemokine (C—X—C G-protein coupled receptor, 2486 6454 motif) receptor 4 Receptor, Transmembrane, Glycoprotein, Sulfation, Antigen, Alternative splicing NM_003475 C11orf13 chromosome 11 Coiled coil, Alternative splicing 2487 6455 open reading frame 13 NM_003477 PDX1 pyruvate Transit peptide, Mitochondrion, 2488 6456 dehydrogenase Lipoyl, Hypothetical protein, complex, component X Acyltransferase, Transferase NM_003489 NRIP1 nuclear receptor Transcription regulation, Nuclear 2489 6457 interacting protein 1 protein NM_003493 HIST3H3 histone 3, H3 Nuclear protein, Chromosomal 2490 6458 protein, DNA-binding, Nucleosome core, Multigene family, Acetylation, Methylation NM_003494 DYSF dysferlin, limb girdle Transmembrane, Repeat, Disease 2491 6459 muscular dystrophy mutation, Hypothetical protein 2B (autosomal recessive) NM_003498 SNN stannin Transmembrane, Hypothetical 2492 6460 protein NM_003507 FZD7 frizzled homolog 7 Multigene family, G-protein coupled 2493 6461 (Drosophila) receptor, Transmembrane, Developmental protein, Wnt signaling pathway, Glycoprotein, Signal NM_003508 FZD9 frizzled homolog 9 Multigene family, G-protein coupled 2494 6462 (Drosophila) receptor, Transmembrane, Developmental protein, Wnt signaling pathway, Glycoprotein, Signal NM_003530 HIST1H3D histone 1, H3d Nuclear protein, Chromosomal 2495 6463 protein, DNA-binding, Nucleosome core, Multigene family, Acetylation, Methylation NM_003532 HIST1H3E histone 1, H3c Nuclear protein, Chromosomal 2496 6464 protein, DNA-binding, Nucleosome core, Multigene family, Acetylation, Methylation NM_003534 HIST1H3G histone 1, H3g Nuclear protein, Chromosomal 2497 6465 protein, DNA-binding, Nucleosome core, Multigene family, Acetylation, Methylation NM_003535 HIST1H3J histone 1, H3j Nuclear protein, Chromosomal 2498 6466 protein, DNA-binding, Nucleosome core, Multigene family, Acetylation, Methylation NM_003549 HYAL3 hyaluronoglucosaminidase 3 EGE-like domain 2499 6467 NM_003560 PLA2G6 phospholipase A2, Hypothetical protein, ANK repeat, 2500 6468 group VI (cytosolic, Repeat, Hydrolase, Lipid calcium- degradation, Membrane, Alternative independent) splicing NM_003562 SLC25A11 solute carrier family Mitochondrion, Inner membrane, 2501 6469 25 (mitochondrial Repeat, Transmembrane, Transport carrier; oxoglutarate carrier), member 11 NM_003565 ULK1 unc-51-like kinase 1 Hypothetical protein, ATP-binding, 2502 6470 (C. elegans) Transferase, Serine/threonine- protein kinase NM_003570 CMAH MRNA for CMP-N- 2503 6471 acetylneuraminic acid hydroxylase, complete cds. NM_003577 UTF1 undifferentiated 2504 6472 embryonic cell transcription factor 1 NM_003579 RAD54L RAD54-like (S. cerevisiae) ATP-binding, DNA repair, Helicase, 2505 6473 Hydrolase NM_003587 DDX16 DEAH (Asp-Glu-Ala- ATP-binding, Helicase, Hydrolase, 2506 6474 His) box polypeptide mRNA processing, mRNA splicing, 16 Nuclear protein NM_00359 SUPT3H suppressor of Ty 3 Transcription regulation, Activator, 2507 6475 homolog (S. cerevisiae) Nuclear protein, Alternative splicing NM_003601 SMARCA5 SWI/SNF related, ATP-binding, DNA-binding, Helicase, 2508 6476 matrix associated, Hydrolase, Nuclear protein actin dependent regulator of chromatin, subfamily a, member 5 NM_003618 MAP4K3 mitogen-activated ATP-binding, Kinase, Transferase 2509 6477 protein kinase kinase kinase kinase 3 NM_003624 RANBP3 RAN binding protein 3 Hypothetical protein 2510 6478 NM_003634 NIPSNAP1 nipsnap homolog 1 Polymorphism 2511 6479 (C. elegans) NM_003635 NDST2 N-deacetylase/N- Hypothetical protein, Transferase, 2512 6480 sulfotransferase Transmembrane, Glycoprotein, Golgi (heparan stack, Signal-anchor glucosaminyl) 2 NM_003636 KCNAB2 potassium voltage- Ionic channel, Ion transport, 2513 6481 gated channel, Potassium transport, Voltage-gated shaker-related channel, Alternative splicing subfamily, beta member 2 NM_003639 IKBKG inhibitor of kappa Coiled coil, Transcription regulation, 2514 6482 light polypeptide Nuclear protein, Disease mutation, gene enhancer in B- Anhidrotic ectodermal dysplasia, cells, kinase gamma Repeat, LIM domain, Metal-binding, Zinc, Developmental protein, Differentiation, Zinc-finger NM_003644 GAS7 growth arrest- Neurogenesis, Developmental 2515 6483 specific 7 protein, Coiled coil, Proto-oncogene, Chromosomal translocation, Alternative splicing NM_003648 DGKD diacylglycerol Transferase, Kinase, Phorbol-ester 2516 6484 kinase, delta 130 kDa binding, Repeat, Multigene family NM_003650 CST7 cystatin F Thiol protease inhibitor, 2517 6485 (leukocystatin) Glycoprotein, Signal NM_003655 CBX4 chromobox homolog Chromatin regulator, Nuclear 2518 6486 4 (Pc class homolog, protein, Transcription regulation, Drosophila) Repressor, Alternative splicing NM_003668 MAPKAPK5 mitogen-activated Hypothetical protein, ATP-binding, 2519 6487 protein kinase- Kinase, Serine/threonine-protein activated protein kinase, Transferase kinase 5 NM_003674 CDK10 cyclin-dependent Transferase, Serine/threonine- 2520 6488 kinase (CDC2-like) protein kinase, ATP-binding, Kinase, 10 Cyclin NM_003680 YARS tyrosyl-tRNA Aminoacyl-tRNA synthetase, Protein 2521 6489 synthetase biosynthesis, Ligase, ATP-binding, RNA-binding, tRNA-binding, 3D- structure NM_003681 PDXK pyridoxal Transferase, Kinase, Alternative 2522 6490 (pyridoxine, vitamin splicing B6) kinase NM_003682 MADD MAP-kinase Hypothetical protein, Kinase 2523 6491 activating death domain NM_003685 KHSRP KH-type splicing Transport, mRNA transport, mRNA 2524 6492 regulatory protein processing, mRNA splicing, (FUSE binding Transcription regulation, Trans- protein 2) acting factor, Nuclear protein, DNA- binding, RNA-binding, Repeat NM_003686 EXO1 exonuclease 1 Exonuclease, Hypothetical protein 2525 6493 NM_003690 PRKRA protein kinase, Hypothetical protein, Kinase 2526 6494 interferon-inducible double stranded RNA dependent activator NM_003707 RUVBL1 RuvB-like 1 (E. coli) Transcription, DNA recombination, 2527 6495 ATP-binding, Hydrolase, Helicase, Nuclear protein NM_003709 KLF7 Kruppel-like factor 7 Transcription regulation, Activator, 2528 6496 (ubiquitous) Zinc-finger, Metal-binding, DNA- binding, Nuclear protein, Repeat NM_003713 PPAP2B phosphatidic acid Collagen, Hydrolase, Hypothetical 2529 6497 phosphatase type protein 2B NM_003725 RODH 3-hydroxysteroid Oxidoreductase 2530 6498 epimerase NM_003726 SCAP1 src family associated SH3 domain 2531 6499 phosphoprotein 1 NM_003730 RNASE6PL ribonuclease T2 Hydrolase, Nuclease, Endonuclease, 2532 6500 Glycoprotein, Signal, Alternative splicing, Polymorphism, Hypothetical protein NM_003734 AOC3 amine oxidase, Oxidoreductase, Copper, TPQ, 2533 6501 copper containing 3 Glycoprotein, Transmembrane, (vascular adhesion Signal-anchor, Cell adhesion, protein 1) Polymorphism, Metal-binding NM_003748 ALDH4A1 aldehyde Oxidoreductase, NAD, Proline 2534 6502 dehydrogenase 4 metabolism, Mitochondrion, Transit family, member A1 peptide, Polymorphism, Disease mutation NM_003750 EIF3S10 eukaryotic Initiation factor, Protein biosynthesis, 2535 6503 translation initiation Repeat, Phosphorylation factor 3, subunit 10 theta, 150/170 kDa NM_003754 EIF3S5 eukaryotic Initiation factor, Protein biosynthesis, 2536 6504 translation initiation Polymorphism, Hypothetical protein factor 3, subunit 5 epsilon, 47 kDa NM_003755 EIF3S4 eukaryotic Initiation factor, Protein biosynthesis, 2537 6505 translation initiation RNA-binding factor 3, subunit 4 delta, 44 kDa NM_003756 EIF3S3 eukaryotic Initiation factor, Protein biosynthesis 2538 6506 translation initiation factor 3, subunit 3 gamma, 40 kDa NM_003758 EIF3S1 eukaryotic Hypothetical protein, Initiation factor, 2539 6507 translation initiation Protein biosynthesis factor 3, subunit 1 alpha, 35 kDa NM_003764 STX11 syntaxin 11 Coiled coil, Membrane, 2540 6508 Polymorphism NM_003765 STX10 syntaxin 10 Coiled coil, Transmembrane, 2541 6509 Transport, Protein transport, Golgi stack, Alternative splicing NM_003769 SFRS9 splicing factor, Nuclear protein, RNA-binding, 2542 6510 arginine/serine-rich 9 mRNA splicing, Repeat, Phosphorylation NM_003776 MRPL40 mitochondrial Ribosomal protein, Mitochondrion, 2543 6511 ribosomal protein Transit peptide, Polymorphism L40 NM_003782 B3GALT4 UDP- Transferase, Glycosyltransferase, 2544 6512 Gal: betaGlcNAc Glycoprotein, Transmembrane, beta 1,3- Signal-anchor, Golgi stack galactosyltransferase, polypeptide 4 NM_003786 ABCC3 ATP-binding ATP-binding, Glycoprotein, 2545 6513 cassette, sub-family Transmembrane, Transport, Repeat, C (CFTR/MRP), Alternative splicing member 3 NM_003791 MBTPS1 membrane-bound Hydrolase, Protease, Serine 2546 6514 transcription factor protease, Lipid metabolism, protease, site 1 Cholesterol metabolism, Signal, Transmembrane, Endoplasmic reticulum, Golgi stack, Zymogen, Autocatalytic cleavage, Glycoprotein, Calcium NM_003796 C19orf2 chromosome 19 Nuclear protein 2547 6515 open reading frame 2 NM_003801 GPAA1 GPAA1P anchor Hypothetical protein 2548 6516 attachment protein 1 homolog (yeast) NM_003805 CRADD CASP2 and RIPK1 Apoptosis, 3D-structure 2549 6517 domain containing adaptor with death domain NM_003807 TNFSF14 tumor necrosis factor Cytokine, Transmembrane, 2550 6518 (ligand) superfamily, Glycoprotein, Signal-anchor, member 14 Alternative splicing NM_003808 TNFSF13 tumor necrosis factor Cytokine, Immune response, 2551 6519 (ligand) superfamily, Glycoprotein, Alternative splicing member 13 NM_003815 ADAM15 a disintegrin and Hydrolase, Metalloprotease, Zinc, 2552 6520 metalloproteinase Signal, Glycoprotein, Zymogen, domain 15 Transmembrane, EGF-like domain, (metargidin) SH3-binding, Phosphorylation NM_003820 TNFRSF14 tumor necrosis factor Receptor, Transmembrane, 2553 6521 receptor superfamily, Glycoprotein, Repeat, Signal, member 14 Polymorphism, 3D-structure (herpesvirus entry mediator) NM_003829 MPDZ multiple PDZ domain Hypothetical protein 2554 6522 protein NM_003830 SIGLEC5 sialic acid binding Ig- Cell adhesion, Lectin, 2555 6523 like lectin 5 Transmembrane, Signal, Glycoprotein, Immunoglobulin domain, Repeat, Antigen, Polymorphism NM_003841 TNFRSF10C tumor necrosis factor Receptor, Apoptosis, Glycoprotein, 2556 6524 receptor superfamily, Repeat, GPI-anchor, Signal, member 10c, decoy Lipoprotein without an intracellular domain NM_003846 PEX11B peroxisomal 2557 6525 biogenesis factor 11B NM_003852 TIF1 transcriptional Elongation factor, Protein 2558 6526 intermediary factor 1 biosynthesis, GTP-binding, Methylation, Multigene family, Transcription regulation, Repressor, DNA-binding, Bromodomain, Zinc- finger, Alternative splicing, Nuclear protein, Coiled coil, Repeat NM_003853 IL18RAP interleukin 18 Receptor 2559 6527 receptor accessory protein NM_003866 INPP4B inositol Hypothetical protein 2560 6528 polyphosphate-4- phosphatase, type II, 105 kDa NM_003877 SOCS2 suppressor of SH2 domain, Growth regulation, 2561 6529 cytokine signaling 2 Signal transduction inhibitor NM_003887 DDEF2 development and Hypothetical protein, ANK repeat, 2562 6530 differentiation Repeat, SH3 domain enhancing factor 2 NM_003893 LDB1 LIM domain binding 1 DNA-binding, Homeobox, Nuclear 2563 6531 protein NM_003895 SYNJ1 synaptojanin 1 Hydrolase, Alternative splicing, 2564 6532 Repeat, Endocytosis, RNA-binding, Multigene family, Hypothetical protein NM_003896 SIAT9 sialyltransferase 9 Transferase, Glycosyltransferase, 2565 6533 (CMP- Glycoprotein, Transmembrane, NeuAc: lactosylceramide Signal-anchor, Golgi stack alpha-2,3- sialyltransferase; GM3 synthase) NM_003897 IER3 immediate early Glycoprotein, Transmembrane, 2566 6534 response 3 Signal-anchor NM_003899 ARHGEF7 Rho guanine Hypothetical protein, SH3 domain, 2567 6535 nucleotide exchange Guanine-nucleotide releasing factor, factor (GEF) 7 Alternative splicing, 3D-structure NM_003900 SQSTM1 sequestosome 1 Hypothetical protein 2568 6536 NM_003903 CDC16 CDC16 cell division Ubl conjugation pathway, Cell cycle, 2569 6537 cycle 16 homolog (S. cerevisiae) Cell division, Mitosis, Repeat, TPR repeat, Alternative splicing NM_003904 ZNF259 zinc finger protein Nuclear protein, Zinc-finger 2570 6538 259 NM_003905 APPBP1 amyloid beta Hypothetical protein 2571 6539 precursor protein binding protein 1, 59 kDa NM_003909 CPNE3 copine III Repeat, Phosphorylation, 2572 6540 Transferase, Serine/threonine- protein kinase NM_003915 CPNE1 copine I Repeat 2573 6541 NM_003923 FOXH1 forkhead box H1 Transcription regulation, Activator, 2574 6542 DNA-binding, Nuclear protein, Polymorphism NM_003931 WASF1 WAS protein family, Actin-binding 2575 6543 member 1 NM_003938 AP3D1 adaptor-related Golgi stack, Protein transport, 2576 6544 protein complex 3, Transport, Alternative splicing, delta 1 subunit Polymorphism NM_003940 USP13 ubiquitin specific Ubl conjugation pathway, Hydrolase, 2577 6545 protease 13 Thiol protease, Multigene family, (isopeptidase T-3) Repeat, Hypothetical protein NM_003943 GENX- genethonin 1 2578 6546 3414 NM_003945 ATP6V0E ATPase, H+ Hydrolase, Hydrogen ion transport, 2579 6547 transporting, Transmembrane lysosomal 9 kDa, V0 subunit e NM_003951 SLC25A14 solute carrier family Mitochondrion, Repeat, 2580 6548 25 (mitochondrial Transmembrane, Transport, carrier, brain), Alternative splicing member 14 NM_003953 MPZL1 myelin protein zero- Hypothetical protein 2581 6549 like 1 NM_003954 MAP3K14 mitogen-activated Hypothetical protein, Transferase, 2582 6550 protein kinase Serine/threonine-protein kinase, kinase kinase 14 ATP-binding, Phosphorylation NM_003967 PNR putative G-protein coupled receptor, 2583 6551 neurotransmitter Receptor, Transmembrane receptor NM_003975 SH2D2A SH2 domain protein Angiogenesis, Phosphorylation, SH2 2584 6552 2A domain, SH3-binding, Alternative splicing NM_003977 AIP aryl hydrocarbon Repeat, TPR repeat 2585 6553 receptor interacting protein NM_003978 PSTPIP1 proline-serine- SH3 domain 2586 6554 threonine phosphatase interacting protein 1 NM_003983 SLC7A6 solute carrier family Hypothetical protein 2587 6555 7 (cationic amino acid transporter, y+ system), member 6 NM_004031 IRF7 interferon regulatory Transcription regulation, DNA- 2588 6556 factor 7 binding, Nuclear protein, Activator, Alternative splicing, Collagen NM_004033 ANXA6 annexin A6 Annexin, Calcium/phospholipid- 2589 6557 binding, Repeat, Acetylation, Phosphorylation, 3D-structure NM_004037 AMPD2 adenosine Hydrolase, Nucleotide metabolism, 2590 6558 monophosphate Multigene family, Alternative splicing deaminase 2 (isoform L) NM_004039 ANXA2 annexin A2 Annexin, Calcium, Calcium-binding, 2591 6559 Calcium/phospholipid-binding, Repeat, Phosphorylation, Acetylation, Polymorphism NM_004044 ATIC 5-aminoimidazole-4- Purine biosynthesis, Transferase, 2592 6560 carboxamide Hydrolase, Multifunctional enzyme ribonucleotide formyltransferase/IMP cyclohydrolase NM_004046 ATP5A1 ATP synthase, H+ ATP synthesis, ATP-binding, CF(1), 2593 6561 transporting, Hydrogen ion transport, Hydrolase, mitochondrial F1 Ion transport, Transport, complex, alpha Mitochondrion, Transit peptide, subunit, isoform 1, Pyrrolidone carboxylic acid, cardiac muscle Hypothetical protein NM_004047 ATP6V0B ATPase, H+ Hydrolase, Hydrogen ion transport, 2594 6562 transporting, ATP synthesis, Transmembrane lysosomal 21 kDa, V0 subunit c″ NM_004049 BCL2A1 BCL2-related protein Apoptosis 2595 6563 A1 NM_004053 BYSL bystin-like Cell adhesion 2596 6564 NM_004054 C3AR1 complement G-protein coupled receptor, 2597 6565 component 3a Transmembrane, Glycoprotein, receptor 1 Chemotaxis NM_004060 CCNG1 cyclin G1 Cyclin, Cell cycle, Cell division, 2598 6566 Mitosis, Nuclear protein NM_004070 CLCNKA chloride channel Ka Ionic channel, Ion transport, Chloride 2599 6567 channel, Chloride, Voltage-gated channel, Transmembrane, CBS domain, Repeat NM_004073 CNK cytokine-inducible Transferase, Serine/threonine- 2600 6568 kinase protein kinase, ATP-binding, Repeat, Phosphorylation, Hypothetical protein, Kinase NM_004079 CTSS cathepsin S Hydrolase, Thiol protease, 2601 6569 Lysosome, Zymogen, Signal, 3D- structure NM_004084 DEFA1 defensin, alpha 1, Defensin, Antibiotic, Antiviral, 2602 6570 myeloid-related Fungicide, Signal, 3D-structure sequence NM_004090 DUSP3 dual specificity Hydrolase, 3D-structure, 2603 6571 phosphatase 3 Hypothetical protein (vaccinia virus phosphatase VH1- related) NM_004092 ECHS1 enoyl Coenzyme A Fatty acid metabolism, Lyase, 2604 6572 hydratase, short Mitochondrion, Transit peptide chain, 1, mitochondrial NM_004094 EIF2S1 eukaryotic Initiation factor, Protein biosynthesis, 2605 6573 translation initiation Translation regulation, RNA-binding, factor 2, subunit 1 Phosphorylation, 3D-structure alpha, 35 kDa NM_004099 STOM stomatin Erythrocyte, Transmembrane, 2606 6574 Phosphorylation, Lipoprotein, Palmitate, Hypothetical protein, Transducer, Prenylation, Multigene family NM_004105 EFEMP1 EGF-containing Repeat, EGF-like domain, Calcium- 2607 6575 fibulin-like binding, Glycoprotein, Signal, extracellular matrix Disease mutation, Polymorphism, protein 1 Alternative splicing NM_004106 FCER1G Fc fragment of IgE, IgE-binding protein, Receptor, 2608 6576 high affinity I, Transmembrane, Signal receptor for; gamma polypeptide NM_004107 FCGRT Fc fragment of IgG, IgG-binding protein, Receptor, 2609 6577 receptor, transporter, Transmembrane, Glycoprotein, alpha Signal, Immunoglobulin domain, 3D- structure NM_004108 FCN2 ficolin Lectin, Collagen, Repeat, 2610 6578 (collagen/fibrinogen Glycoprotein, Signal, Multigene domain containing family lectin) 2 (hucolin) NM_004109 FDX1 ferredoxin 1 Metal-binding, Iron-sulfur, Iron, 2Fe—2S, 2611 6579 Electron transport, Mitochondrion, Transit peptide NM_004115 FGF14 fibroblast growth Growth factor 2612 6580 factor 14 NM_004119 FLT3 fms-related tyrosine Signal, Transferase, Tyrosine- 2613 6581 kinase 3 protein kinase, Receptor, Transmembrane, Glycoprotein, Phosphorylation, ATP-binding, Immunoglobulin domain NM_004122 GHSR growth hormone G-protein coupled receptor, 2614 6582 secretagogue Transmembrane, Glycoprotein, receptor Alternative splicing NM_004126 GNG11 guanine nucleotide Transducer, Prenylation, Lipoprotein, 2615 6583 binding protein (G Multigene family protein), gamma 11 NM_004128 GTF2F2 general transcription Transcription regulation, DNA- 2616 6584 factor IIF, binding, Helicase, ATP-binding, polypeptide 2, Nuclear protein, 3D-structure 30 kDa NM_004130 GYG glycogenin Transferase, Glycogen biosynthesis, 2617 6585 Acetylation, Phosphorylation, Glycoprotein, Alternative splicing, Hypothetical protein NM_004131 GZMB granzyme B Hydrolase, Serine protease, 2618 6586 (granzyme 2, Zymogen, Signal, T-cell, Cytolysis, cytotoxic T- Apoptosis, Glycoprotein, 3D- lymphocyte- structure, Protease associated serine esterase 1) NM_004134 HSPA9B heat shock 70 kDa ATP-binding, Heat shock, 2619 6587 protein 9B (mortalin- Chaperone, Mitochondrion, Transit 2) peptide NM_004147 DRG1 developmentally GTP-binding, Hypothetical protein 2620 6588 regulated GTP binding protein 1 NM_004148 NINJ1 ninjurin 1 Cell adhesion, Transmembrane, 2621 6589 Hypothetical protein NM_004152 OAZ1 ornithine 2622 6590 decarboxylase antizyme 1 NM_004168 SDHA succinate Tricarboxylic acid cycle, 2623 6591 dehydrogenase Flavoprotein, FAD, Oxidoreductase, complex, subunit A, Electron transport, Mitochondrion, flavoprotein (Fp) Transit peptide, Disease mutation, Leigh syndrome NM_004177 STX3A syntaxin 3A Neurotransmitter transport, Coiled 2624 6592 coil, Transmembrane, Alternative splicing NM_004178 TARBP2 TAR (HIV) RNA Hypothetical protein, RNA-binding, 2625 6593 binding protein 2 Repeat, Nuclear protein NM_004180 TANK TRAF family Zinc-finger, Metal-binding, 2626 6594 member-associated Alternative splicing, 3D-structure NFKB activator NM_004183 VMD2 vitelliform macular Transport, Ion transport, Ionic 2627 6595 dystrophy (Best channel, Chloride channel, Chloride, disease, bestrophin) Calcium, Alternative splicing, Disease mutation, Polymorphism, Vision, Transmembrane, Phosphorylation, Iron storage, Metal- binding, 3D-structure NM_004207 SLC16A3 solute carrier family Transport, Symport, 2628 6596 16 (monocarboxylic Transmembrane, Multigene family acid transporters), member 3 NM_004221 NK4 natural killer cell Signal 2629 6597 transcript 4 NM_004225 MFHAS1 malignant fibrous GTP-binding 2630 6598 histiocytoma amplified sequence 1 NM_004235 KLF4 Kruppel-like factor 4 Transcription regulation, Activator, 2631 6599 (gut) Zinc-finger, Metal-binding, DNA- binding, Nuclear protein, Repeat NM_004239 TRIP11 thyroid hormone Hypothetical protein, Antigen, Golgi 2632 6600 receptor interactor stack, Coiled coil, Chromosomal 11 translocation NM_004244 CD163 CD163 antigen Signal, Antigen 2633 6601 NM_004245 TGM5 transglutaminase 5 Transferase, Acyltransferase, 2634 6602 Calcium-binding, Polymorphism, Alternative splicing NM_004252 SLC9A3R1 solute carrier family 2635 6603 9 (sodium/hydrogen exchanger), isoform 3 regulatory factor 1 NM_004255 COX5A cytochrome c Oxidoreductase, Heme, 2636 6604 oxidase subunit Va Mitochondrion, Inner membrane, Transit peptide NM_004258 IGSF2 immunoglobulin 2637 6605 superfamily, member 2 NM_004263 SEMA4F sema domain, Signal, Transmembrane, 2638 6606 immunoglobulin Immunoglobulin domain, Multigene domain (Ig), family, Neurogenesis, transmembrane Developmental protein, domain (TM) and Glycoprotein, Alternative splicing short cytoplasmic domain, (semaphorin) 4F NM_004265 FADS2 fatty acid desaturase 2 Hypothetical protein, Heme 2639 6607 NM_004272 HOMER1 homer homolog 1 Coiled coil, Alternative splicing 2640 6608 (Drosophila) NM_004279 PMPCB peptidase Chaperone, Nuclear protein, 2641 6609 (mitochondrial Phosphorylation, Hydrolase, processing) beta Metalloprotease, Zinc, Mitochondrion, Transit peptide, Hypothetical protein NM_004295 TRAF4 TNF receptor- Apoptosis, Developmental protein, 2642 6610 associated factor 4 Nuclear protein, Zinc-finger, Coiled coil, Repeat, Alternative splicing NM_004300 ACP1 acid phosphatase 1, Hydrolase, Acetylation, Alternative 2643 6611 soluble splicing, Polymorphism, 3D-structure NM_004305 BIN1 bridging integrator 1 Alternative splicing, SH3 domain, 2644 6612 Coiled coil, Endocytosis, Anti- oncogene, Differentiation, Phosphorylation, Hypothetical protein NM_004309 ARHGDIA Rho GDP GTPase activation, 3D-structure 2645 6613 dissociation inhibitor (GDI) alpha NM_004313 ARRB2 arrestin, beta 2 Sensory transduction, Nuclear 2646 6614 protein, Alternative splicing NM_004331 BNIP3L BCL2/adenovirus Apoptosis, Transmembrane, 2647 6615 E1B 19 kDa Mitochondrion interacting protein 3- like NM_004334 BST1 bone marrow Hydrolase, NAD, Glycoprotein, GPI- 2648 6616 stromal cell antigen 1 anchor, Signal, 3D-structure, Lipoprotein, Hypothetical protein NM_004336 BUB1 BUB1 budding Transferase, Serine/threonine- 2649 6617 uninhibited by protein kinase, ATP-binding, Cell benzimidazoles 1 cycle, Nuclear protein, Mitosis, homolog (yeast) Phosphorylation, Polymorphism NM_004337 C8orf1 chromosome 8 open Meiosis 2650 6618 reading frame 1 NM_004345 CAMP cathelicidin Antibiotic, Signal, Pyrrolidone 2651 6619 antimicrobial peptide carboxylic acid NM_004350 RUNX3 runt-related Transcription regulation, DNA- 2652 6620 transcription factor 3 binding, Nuclear protein, ATP- binding, Alternative splicing NM_004358 CDC25B cell division cycle Cell division, Mitosis, Hydrolase, 2653 6621 25B Alternative splicing, Multigene family, 3D-structure NM_004360 CDH1 cadherin 1, type 1, Elongation factor, Protein 2654 6622 E-cadherin biosynthesis, GTP-binding, (epithelial) Methylation, Multigene family, Ribosomal protein, Repeat, Hypothetical protein, Cell adhesion, Glycoprotein, Transmembrane, Calcium-binding, Signal, Phosphorylation, Disease mutation, Polymorphism, 3D-structure NM_004368 CNN2 calponin 2 Calmodulin-binding, Actin-binding, 2655 6623 Multigene family, Repeat NM_004374 COX6C cytochrome c Oxidoreductase, Inner membrane, 2656 6624 oxidase subunit VIc Mitochondrion NM_004375 COX11 COX11 homolog, Copper, Mitochondrion, 2657 6625 cytochrome c Transmembrane, Transit peptide, oxidase assembly Transport, Protein transport, SH3- protein (yeast) binding, Membrane, Golgi stack, Phosphorylation, Hypothetical protein NM_004380 CREBBP CREB binding Transferase, Transcription 2658 6626 protein (Rubinstein- regulation, Nuclear protein, Taybi syndrome) Activator, Bromodomain, Chromosomal translocation, Zinc- finger, Repeat, Disease mutation, 3D-structure NM_004381 CREBL1 cAMP responsive Glycoprotein, Cell adhesion, Repeat, 2659 6627 element binding EGF-like domain, Coiled coil, protein-like 1 Extracellular matrix, Alternative splicing, Signal, Ehlers-Danlos syndrome, Transcription regulation, DNA-binding, Activator, Unfolded protein response, Nuclear protein, Endoplasmic reticu NM_004385 CSPG2 chondroitin sulfate Glycoprotein, Proteoglycan, Lectin, 2660 6628 proteoglycan 2 Extracellular matrix, Sushi, Signal, (versican) Repeat, EGF-like domain, Calcium, Immunoglobulin domain, Hyaluronic acid, Alternative splicing NM_004390 CTSH cathepsin H Hydrolase, Protease, Thiol protease, 2661 6629 Lysosome, Glycoprotein, Zymogen, Signal, 3D-structure NM_004398 DDX10 DEAD (Asp-Glu-Ala- Helicase, ATP-binding, RNA-binding 2662 6630 Asp) box polypeptide 10 NM_004409 DMPK dystrophia Transferase, Serine/threonine- 2663 6631 myotonica-protein protein kinase, ATP-binding, Coiled kinase coil, Alternative splicing NM_004417 DUSP1 dual specificity Hydrolase, Cell cycle 2664 6632 phosphatase 1 NM_004418 DUSP2 dual specificity Hydrolase, Nuclear protein, 3D- 2665 6633 phosphatase 2 structure NM_004424 E4F1 E4F transcription Metal-binding, Zinc, Zinc-finger 2666 6634 factor 1 NM_004427 PHC2 polyhomeotic-like 2 Hypothetical protein 2667 6635 (Drosophila) NM_004446 EPRS glutamyl-prolyl-tRNA Aminoacyl-tRNA synthetase, Protein 2668 6636 synthetase biosynthesis, Ligase, ATP-binding, Multifunctional enzyme, Repeat, 3D- structure NM_004450 ERH enhancer of 2669 6637 rudimentary homolog (Drosophila) NM_004453 ETFDH electron-transferring- Oxidoreductase, Electron transport, 2670 6638 flavoprotein Flavoprotein, FAD, Iron-sulfur, 4Fe—4S, dehydrogenase Mitochondrion, Transit peptide, Ubiquinone, Transmembrane, Glutaricaciduria NM_004475 FLOT2 flotillin 2 Cell adhesion, Membrane 2671 6639 NM_004477 FRG1 FSHD region gene 1 Multigene family 2672 6640 NM_004479 FUT7 fucosyltransferase 7 Transferase, Glycosyltransferase, 2673 6641 (alpha (1, 3) Transmembrane, Glycoprotein, fucosyltransferase) Signal-anchor, Golgi stack NM_004480 FUT8 fucosyltransferase 8 Transferase, Glycosyltransferase, 2674 6642 (alpha (1, 6) Transmembrane, Signal-anchor, fucosyltransferase) Golgi stack, SH3 domain, SH3- binding, Alternative splicing NM_004482 GALNT3 UDP-N-acetyl-alpha- Transferase 2675 6643 D- galactosamine:polypeptide N- acetylgalactosaminyl transferase 3 (GalNAc-T3) NM_004483 GCSH glycine cleavage Mitochondrion, Transit peptide, 2676 6644 system protein H Lipoyl (aminomethyl carrier) NM_004485 GNG4 guanine nucleotide Transducer, Prenylation, Lipoprotein, 2677 6645 binding protein (G Multigene family protein), gamma 4 NM_004489 GPS2 G protein pathway Hypothetical protein 2678 6646 suppressor 2 NM_004492 GTF2A2 general transcription Transcription regulation, Nuclear 2679 6647 factor IIA, 2, 12 kDa protein NM_004497 FOXA3 forkhead box A3 DNA-binding, Nuclear protein, 2680 6648 Transcription regulation, Activator, Polymorphism NM_004504 HRB HIV-1 Rev binding Nuclear protein, Transport, Repeat, 2681 6649 protein DNA-binding, Zinc-finger NM_004506 HSF2 heat shock Heat shock, Transcription regulation, 2682 6650 transcription factor 2 Nuclear protein, DNA-binding, Activator, Phosphorylation, Multigene family NM_004513 IL16 interleukin 16 Cytokine, Chemotaxis, Repeat, 3D- 2683 6651 (lymphocyte structure chemoattractant factor) NM_004515 ILF2 interleukin enhancer 2684 6652 binding factor 2, 45 kDa NM_004516 ILF3 interleukin enhancer Hypothetical protein, Transcription 2685 6653 binding factor 3, regulation, DNA-binding, RNA- 90 kDa binding, Nuclear protein, Repeat, Phosphorylation, Methylation, Alternative splicing NM_004524 LLGL2 lethal giant larvae Repeat, WD repeat 2686 6654 homolog 2 (Drosophila) NM_004529 MLLT3 myeloid/lymphoid or Transcription regulation, Activator, 2687 6655 mixed-lineage Nuclear protein, Chromosomal leukemia (trithorax translocation, Proto-oncogene homolog, Drosophila); translocated to, 3 NM_004537 NAP1L1 nucleosome Nuclear protein 2688 6656 assembly protein 1- like 1 NM_004554 NFATC4 nuclear factor of Hypothetical protein, Transcription 2689 6657 activated T-cells, regulation, Activator, Nuclear cytoplasmic, protein, DNA-binding, Repeat, calcineurin- Phosphorylation dependent 4 NM_004563 PCK2 phosphoenolpyruvate Gluconeogenesis, Lyase, 2690 6658 carboxykinase 2 Decarboxylase, GTP-binding, (mitochondrial) Mitochondrion, Transit peptide, Manganese NM_004566 PFKFB3 6-phosphofructo-2- Kinase, Hydrolase, Multifunctional 2691 6659 kinase/fructose-2,6- enzyme, Transferase, ATP-binding, biphosphatase 3 Phosphorylation, Multigene family, Alternative splicing NM_004569 PIGH phosphatidylinositol Hypothetical protein, Transferase, 2692 6660 glycan, class H Glycosyltransferase NM_004573 PLCB2 phospholipase C, Hydrolase, Lipid degradation, 2693 6661 beta 2 Transducer, Calcium NM_004578 RAB4A RAB4A, member GTP-binding, Lipoprotein, 2694 6662 RAS oncogene Prenylation, Protein transport, family Phosphorylation NM_004580 RAB27A RAB27A, member GTP-binding, Lipoprotein, 2695 6663 RAS oncogene Prenylation, Alternative splicing, family Disease mutation NM_004583 RAB5C RAB5C, member GTP-binding, Lipoprotein, 2696 6664 RAS oncogene Prenylation, Protein transport family NM_004603 STX1A syntaxin 1A (brain) Neurotransmitter transport, Coiled 2697 6665 coil, Transmembrane, Antigen, Alternative splicing, Williams-Beuren syndrome NM_004618 TOP3A topoisomerase Isomerase, Topoisomerase, DNA- 2698 6666 (DNA) III alpha binding, Repeat, Zinc-finger, Alternative splicing, Polymorphism NM_004629 FANCG Fanconi anemia, DNA repair, Nuclear protein 2699 6667 complementation group G NM_004632 DAP3 death associated Apoptosis, Ribosomal protein, 2700 6668 protein 3 Mitochondrion NM_004633 IL1R2 interleukin 1 Immunoglobulin domain, Receptor, 2701 6669 receptor, type II Glycoprotein, Transmembrane, Signal, Repeat NM_004635 MAPKAPK3 mitogen-activated ATP-binding, Kinase, 2702 6670 protein kinase- Serine/threonine-protein kinase, activated protein Transferase kinase 3 NM_004637 RAB7 RAB7, member RAS GTP-binding, Lipoprotein, 2703 6671 oncogene family Prenylation, Protein transport, Hypothetical protein NM_004642 CDK2AP1 CDK2-associated Anti-oncogene 2704 6672 protein 1 NM_004648 PTPNS1 protein tyrosine Repeat, Signal, Transmembrane, 2705 6673 phosphatase, non- Immunoglobulin domain, SH3- receptor type binding, Glycoprotein, substrate 1 Phosphorylation, Alternative splicing, Polymorphism NM_004651 USP11 ubiquitin specific Ubl conjugation pathway, Hydrolase, 2706 6674 protease 11 Thiol protease, Nuclear protein, Multigene family NM_004664 LIN7A lin-7 homolog A (C. elegans) 2707 6675 NM_004665 VNN2 vanin 2 Hydrolase, Signal, Glycoprotein, 2708 6676 GPI-anchor, Lipoprotein NM_004666 VNN1 vanin 1 Hydrolase, Signal, Glycoprotein, 2709 6677 GPI-anchor, Lipoprotein NM_004668 MGAM maltase- Multifunctional enzyme, 2710 6678 glucoamylase Transmembrane, Glycoprotein, (alpha-glucosidase) Hydrolase, Glycosidase, Repeat, Signal-anchor, Sulfation NM_004682 PSIP2 PC4 and SFRS1 2711 6679 interacting protein 1 NM_004689 MTA1 metastasis Zinc-finger, Nuclear protein, 2712 6680 associated 1 Alternative splicing NM_004694 SLC16A6 solute carrier family Transport, Symport, 2713 6681 16 (monocarboxylic Transmembrane, Multigene family acid transporters), member 6 NM_004706 ARHGEF1 Rho guanine Guanine-nucleotide releasing factor, 2714 6682 nucleotide exchange GTPase activation, Coiled coil, factor (GEF) 1 Alternative splicing, Phosphorylation, 3D-structure NM_004708 PDCD5 programmed cell Apoptosis 2715 6683 death 5 NM_004712 HGS hepatocyte growth Kinase 2716 6684 factor-regulated tyrosine kinase substrate NM_004720 EDG4 endothelial G-protein coupled receptor, 2717 6685 differentiation, Transmembrane, Glycoprotein, lysophosphatidic Multigene family, Lipoprotein, acid G-protein- Palmitate coupled receptor, 4 NM_004726 REPS2 RALBP1 associated Calcium-binding, Coiled coil, 2718 6686 Eps domain Phosphorylation, Alternative splicing, containing 2 Repeat, 3D-structure NM_004727 SLC24A1 solute carrier family Vision, Transport, Antiport, Symport, 2719 6687 24 Calcium transport, Transmembrane, (sodium/potassium/calcium Glycoprotein, Phosphorylation, exchanger), Signal, Repeat, Alternative splicing member 1 NM_004729 ALTE Ac-like transposable 2720 6688 element NM_004741 NOLC1 nucleolar and coiled- Nuclear protein, Phosphorylation, 2721 6689 body phosphoprotein 1 Repeat, GTP-binding, ATP-binding, Alternative splicing NM_004748 CPR8 cell cycle Hypothetical protein 2722 6690 progression 8 protein NM_004749 CPR2 cell cycle Hypothetical protein 2723 6691 progression 2 protein NM_004756 NUMBL numb homolog 2724 6692 (Drosophila)-like NM_004757 SCYE1 small inducible Protein biosynthesis, RNA-binding, 2725 6693 cytokine subfamily tRNA-binding, Cytokine, 3D- E, member 1 structure (endothelial monocyte-activating) NM_004762 PSCD1 pleckstrin homology, Guanine-nucleotide releasing factor, 2726 6694 Sec7 and coiled-coil Coiled coil, Alternative splicing, 3D- domains 1 (cytohesin 1) structure NM_004774 PPARBP PPAR binding DNA-binding, Transcription 2727 6695 protein regulation, Activator, Repeat, Nuclear protein, Alternative splicing NM_004779 CNOT8 CCR4-NOT Coiled coil, Nuclear protein, 2728 6696 transcription Alternative splicing, Hypothetical complex, subunit 8 protein, Molybdenum cofactor biosynthesis, Disease mutation, Transcription regulation, Repressor NM_004781 VAMP3 vesicle-associated Synapse, Synaptosome, 2729 6697 membrane protein 3 Transmembrane, Coiled coil, (cellubrevin) Multigene family NM_004786 TXNL thioredoxin-like, Redox-active center, Electron 2730 6698 32 kDa transport, 3D-structure NM_004800 TM9SF2 transmembrane 9 Signal, Transmembrane 2731 6699 superfamily member 2 NM_004802 OTOF otoferlin Transmembrane, Repeat, Alternative 2732 6700 splicing, Deafness NM_004808 NMT2 N- Transferase, Acyltransferase 2733 6701 myristoyltransferase 2 NM_004814 HPRP8BP U5 snRNP-specific Repeat, WD repeat, Hypothetical 2734 6702 40 kDa protein protein (hPrp8-binding) NM_004817 TJP2 tight junction protein Tight junction, SH3 domain, Repeat, 2735 6703 2 (zona occludens 2) Membrane, Alternative splicing, Alternative promoter usage, Nuclear protein, Phosphorylation NM_004834 MAP4K4 mitogen-activated ATP-binding, Serine/threonine- 2736 6704 protein kinase protein kinase, Transferase, kinase kinase kinase 4 Alternative splicing NM_004848 C1orf38 chromosome 1 open Hypothetical protein 2737 6705 reading frame 38 NM_004854 CHST10 carbohydrate Transferase 2738 6706 sulfotransferase 10 NM_004856 KIF23 anaphase-promoting Motor protein, Cell division, 2739 6707 complex subunit 7 Microtubule, ATP-binding, Coiled coil, Mitosis, Cell cycle, Nuclear protein NM_004862 LITAF lipopolysaccharide- Hypothetical protein, Transcription 2740 6708 induced TNF factor regulation, Nuclear protein NM_004868 GPSN2 glycoprotein, Transmembrane, Glycoprotein, 2741 6709 synaptic 2 Alternative splicing NM_004875 POLR1C polymerase (RNA) I Hypothetical protein, Transferase, 2742 6710 polypeptide C, DNA-directed RNA polymerase, 30 kDa Transcription, Nuclear protein, Alternative splicing NM_004877 GMFG glia maturation Growth factor, Ribosomal protein 2743 6711 factor, gamma NM_004878 PTGES prostaglandin E Hypothetical protein, 2744 6712 synthase Transmembrane NM_004879 EI24 etoposide induced 2745 6713 2.4 mRNA NM_004889 ATP5J2 ATP synthase, H+ ATP synthesis, Hydrogen ion 2746 6714 transporting, transport, CF(0), Mitochondrion, mitochondrial F0 Acetylation, Alternative splicing complex, subunit f, isoform 2 NM_004900 APOBEC3B apolipoprotein B Hydrolase 2747 6715 mRNA editing enzyme, catalytic polypeptide-like 3B NM_004900 RNPC2 RNA-binding region Transcription regulation, Activator, 2748 6716 (RNP1, RRM) Nuclear protein, RNA-binding, containing 2 mRNA-processing, mRNA splicing, Repeat, Altemative splicing, Polymorphism NM_004905 PRDX6 peroxiredoxin 6 Hydrolase, Oxidoreductase, 2749 6717 Peroxidase, Lipid degradation, Antioxidant, Redox-active center, Multifunctional enzyme, Lysosome, 3D-structure NM_004907 ETR101 immediate early ATP-binding, Coiled coil, 2750 6718 protein Microtubules, Motor protein NM_004910 PITPNM1 phosphatidylinositol Hypothetical protein 2751 6719 transfer protein, membrane- associated 1 NM_004915 ABCG1 ATP-binding ATP-binding, Transport, Hypothetical 2752 6720 cassette, sub-family protein, Lipid transport, G (WHITE), member 1 Transmembrane, Alternative splicing, Polymorphism NM_004916 WWOX Human Oxidoreductase 2753 6721 oxidoreductase (HHCMA56) mRNA, complete cds. NM_004920 AATK apoptosis- Kinase, Hypothetical protein, ATP- 2754 6722 associated tyrosine binding, Transferase kinase NM_004924 ACTN4 actinin, alpha 4 Actin-binding, Calcium-binding, 2755 6723 Repeat, Multigene family, Disease mutation, Nuclear protein, Hypothetical protein NM_004928 C21orf2 chromosome 21 Alternative splicing, Polymorphism 2756 6724 open reading frame 2 NM_004930 CAPZB capping protein Cytoskeleton, Actin-binding, 2757 6725 (actin filament) Alternative splicing, Actin capping muscle Z-line, beta NM_004939 DDX1 DEAD (Asp-Glu-Ala- Hydrolase, ATP-binding, Helicase, 2758 6726 Asp) box polypeptide 1 RNA-binding NM_004945 DNM2 dynamin 2 Hydrolase, Motor protein, GTP- 2759 6727 binding, Microtubule, Multigene family, Endocytosis, Alternative splicing, Hypothetical protein NM_004954 MARK2 MAP/microtubule ATP-binding, Kinase, 2760 6728 affinity-regulating Serine/threonine-protein kinase, kinase 2 Transferase NM_004974 KCNA2 potassium voltage- Transport, Ion transport, Ionic 2761 6729 gated channel, channel, Voltage-gated channel, shaker-related Potassium channel, Potassium subfamily, member 2 transport, Potassium, Transmembrane, Glycoprotein, Phosphorylation, Multigene family NM_004979 KCND1 potassium voltage- Transport, Ion transport, Ionic 2762 6730 gated channel, Shal- channel, Voltage-gated channel, related subfamily, Potassium channel, Potassium member 1 transport, Potassium, Transmembrane, Multigene family NM_004994 MMP9 matrix Hydrolase, Metalloprotease, 2763 6731 metalloproteinase 9 Glycoprotein, Zinc, Zymogen, (gelatinase B, 92 kDa Calcium, Collagen degradation, gelatinase, 92 kDa Extracellular matrix, Repeat, Signal, type IV collagenase) Polymorphism, 3D-structure NM_005000 NDUFA5 NADH Hypothetical protein, 2764 6732 dehydrogenase Oxidoreductase, NAD, Ubiquinone, (ubiquinone) 1 alpha Mitochondrion, Acetylation subcomplex, 5, 13 kDa NM_005003 NDUFAB1 NADH Fatty acid biosynthesis, 2765 6733 dehydrogenase Phosphopantetheine, Mitochondrion, (ubiquinone) 1, Transit peptide, Oxidoreductase alpha/beta subcomplex, 1, 8 kDa NM_005009 NME4 non-metastatic cells Transferase, Kinase, ATP-binding, 2766 6734 4, protein expressed Mitochondrion, Transit peptide, 3D- in structure NM_005011 NRF1 nuclear respiratory Transcription regulation, DNA- 2767 6735 factor 1 binding, Activator, Nuclear protein, Phosphorylation, Alternative splicing NM_005022 PFN1 profilin 1 Actin-binding, Cytoskeleton, 2768 6736 Multigene family, Acetylation, 3D- structure NM_005024 SERPINB10 serine (or cysteine) Serpin, Serine protease inhibitor 2769 6737 proteinase inhibitor, clade B (ovalbumin), member 10 NM_005025 SERPINI1 serine (or cysteine) Serpin, Serine protease inhibitor, 2770 6738 proteinase inhibitor, Glycoprotein, Signal, Disease clade I mutation (neuroserpin). member 1 NM_005026 PIK3CD phosphoinositide-3- Kinase, Transferase, Multigene 2771 6739 kinase, catalytic, family delta polypeptide NM_005029 PITX3 paired-like Homeobox, DNA-binding, 2772 6740 homeodomain Developmental protein, Nuclear transcription factor 3 protein, Disease mutation NM_005030 PLK polo-like kinase Transferase, Serine/threonine- 2773 6741 (Drosophila) protein kinase, ATP-binding, Repeat, Nuclear protein, Phosphorylation NM_005040 PRCP prolylcarboxypeptidase Hydrolase, Carboxypeptidase, 2774 6742 (angiotensinase Glycoprotein, Zymogen, Signal, C) Lysosome NM_005044 PRKX protein kinase, X- ATP-binding, Kinase, 2775 6743 linked Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase, cAMP NM_005055 RAPSN receptor-associated Synapse, Postsynaptic membrane, 2776 6744 protein of the Cytoskeleton, Phosphorylation, synapse, 43 kD Myristate, Zinc-finger, Repeat, TPR repeat, Alternative splicing, Lipoprotein, Metal-binding, Receptor NM_005056 RBBP2 retinoblastoma Trans-acting factor, Nuclear protein, 2777 6745 binding protein 2 Repeat, Zinc-finger NM_005061 RPL3L ribosomal protein Ribosomal protein 2778 6746 L3-like NM_005066 SFPQ splicing factor Nuclear protein, RNA-binding, DNA- 2779 6747 proline/glutamine binding, mRNA splicing, Repeat, rich (polypyrimidine Alternative splicing tract binding protein associated) NM_005084 PLA2G7 phospholipase A2, Hydrolase, Lipid degradation, 2780 6748 group VII (platelet- Glycoprotein, Signal, Polymorphism, activating factor Disease mutation acetylhydrolase, plasma) NM_005085 NUP214 nucleoporin 214 kDa Hypothetical protein, Repeat, WD 2781 6749 repeat, Nuclear protein, Transport, Proto-oncogene, Chromosomal translocation, Glycoprotein NM_005091 PGLYRP peptidoglycan Antibiotic, Immune response, Signal 2782 6750 recognition protein NM_005096 ZNF261 zinc finger protein Hypothetical protein, Chromosomal 2783 6751 261 translocation, Transmembrane, Alternative splicing NM_005099 ADAMTS4 a disintegrin-like and Hydrolase, Metalloprotease, Zinc, 2784 6752 metalloprotease Signal, Glycoprotein, Zymogen, (reprolysin type) with Extracellular matrix, Hypothetical thrombospondin type protein 1 motif, 4 NM_005106 DLEC1 deleted in lung and Hypothetical protein 2785 6753 esophageal cancer 1 NM_005111 CRYZL1 crystallin, zeta Oxidoreductase, NADP, Alternative 2786 6754 (quinone reductase)- splicing like 1 NM_005112 WDR1 WD repeat domain 1 Repeat, WD repeat, Hypothetical 2787 6755 protein, Actin-binding, Cytoskeleton, Alternative splicing, Polymorphism NM_005134 PPP4R1 protein phosphatase Hypothetical protein 2788 6756 4, regulatory subunit 1 NM_005137 DGCR2 DiGeorge syndrome Cell adhesion, Receptor, Signal, 2789 6757 critical region gene 2 Transmembrane, Lectin, Glycoprotein NM_005139 ANXA3 annexin A3 Annexin, Calcium/phospholipid- 2790 6758 binding, Repeat, Phospholipase A2 inhibitor, 3D-structure, Polymorphism NM_005143 HP haptoglobin Glycoprotein, Serine protease 2791 6759 homolog, Sushi, Hemoglobin- binding, Signal, Repeat, Polymorphism NM_005148 UNC119 unc-119 homolog (C. elegans) Vision, Alternative splicing 2792 6760 NM_005151 USP14 ubiquitin specific Ubl conjugation pathway, Hydrolase, 2793 6761 protease 14 (tRNA- Thiol protease, Multigene family guanine transglycosylase) NM_005165 ALDOC aldolase C, fructose- Lyase, Schiff base, Glycolysis, 2794 6762 bisphosphate Multigene family NM_005167 ARHC hypothetical protein DNA condensation, Mitosis, Cell 2795 6763 MGC19531 cycle, ATP-binding, Coiled coil, Nuclear protein, Alternative splicing, Hypothetical protein, Proto- oncogene, GTP-binding, Prenylation, Lipoprotein NM_005173 ATP2A3 ATPase, Ca++ Hydrolase, Calcium transport, 2796 6764 transporting, Transmembrane, Phosphorylation, ubiquitous ATP-binding, Metal-binding, Magnesium, Calcium-binding, Multigene family, Alternative splicing NM_005174 ATP5C1 ATP synthase, H+ ATP synthesis, CF(1), Hydrogen ion 2797 6765 transporting, transport, Hydrolase, Mitochondrion, mitochondrial F1 Transit peptide, Alternative splicing, complex, gamma Hypothetical protein polypeptide 1 NM_005180 BMI1 B lymphoma Mo- Chromatin regulator, Nuclear 2798 6766 MLV insertion region protein, Transcription regulation, (mouse) Repressor, Zinc-finger, Proto- oncogene NM_005185 CALML3 calmodulin-like 3 Calcium-binding, Repeat, 2799 6767 Methylation, 3D-structure NM_005190 CCNC cyclin C Cyclin, Cell cycle, Cell division, 2800 6768 Nuclear protein, Transcription regulation NM_005195 CEBPD KIAA0146 protein Transcription regulation, Activator, 2801 6769 DNA-binding, Nuclear protein NM_005197 CHES1 checkpoint Transcription regulation, Activator, 2802 6770 suppressor 1 DNA-binding, Nuclear protein, Alternative splicing NM_005199 CHRNG cholinergic receptor, Receptor, Postsynaptic membrane, 2803 6771 nicotinic, gamma Ionic channel, Glycoprotein, Signal, polypeptide Transmembrane NM_005213 CSTA cystatin A (stefin A) Thiol protease inhibitor, 3D-structure 2804 6772 NM_005217 DEFA3 defensin, alpha 3, Defensin, Antibiotic, Antiviral, 2805 6773 neutrophil-specific Fungicide, Signal, 3D-structure NM_005224 DRIL1 dead ringer-like 1 Transcription regulation, Activator, 2806 6774 (Drosophila) DNA-binding, Nuclear protein NM_005231 EMS1 ems1 sequence Phosphorylation, Repeat, SH3 2807 6775 (mammary tumor domain, Cytoskeleton and squamous cell carcinoma- associated (p80/85 src substrate) NM_005239 ETS2 v-ets Proto-oncogene, DNA-binding, 2808 6776 erythroblastosis Nuclear protein virus E26 oncogene homolog 2 (avian) NM_005248 FGR Gardner-Rasheed Transferase, Tyrosine-protein 2809 6777 feline sarcoma viral kinase, Proto-oncogene, ATP- (v-fgr) oncogene binding, Phosphorylation, SH2 homolog domain, SH3 domain NM_005252 FOS v-fos FBJ murine Proto-oncogene, Nuclear protein, 2810 6778 osteosarcoma viral Phosphorylation, DNA-binding, 3D- oncogene homolog structure NM_005253 FOSL2 FOS-like antigen 2 Nuclear protein, DNA-binding 2811 6779 NM_005255 GAK cyclin G associated Transferase, Serine/threonine- 2812 6780 kinase protein kinase, ATP-binding, Nuclear protein, Endoplasmic reticulum, Cell cycle NM_005256 GAS2 growth arrest- Growth arrest, Phosphorylation, 2813 6781 specific 2 Apoptosis, Cell cycle, Cytoskeleton NM_005263 GFI1 growth factor Transcription regulation, Zinc-finger, 2814 6782 independent 1 DNA-binding, Nuclear protein, Metal- binding, Repeat, Disease mutation NM_005270 GLI2 GLI-Kruppel family Transcription regulation, Zinc-finger, 2815 6783 member GLI2 Metal-binding, DNA-binding, Nuclear protein, Repeat, Alternative splicing NM_005271 GLUD1 glutamate Oxidoreductase, NADP, 2816 6784 dehydrogenase 1 Mitochondrion, Transit peptide, Polymorphism, Disease mutation, Multigene family, 3D-structure NM_005273 GNB2 guanine nucleotide Transducer, Repeat, WD repeat, 2817 6785 binding protein (G Multigene family protein), beta polypeptide 2 NM_005274 GNG5 guanine nucleotide Transducer, Prenylation, Lipoprotein, 2818 6786 binding protein (G Multigene family protein), gamma 5 NM_005286 GPR8 G protein-coupled Transcription regulation, Zinc-finger, 2819 6787 receptor 8 DNA-binding, Nuclear protein, Repeat, G-protein coupled receptor, Transmembrane, Glycoprotein, Lipoprotein, Palmitate, Phosphorylation, Polymorphism NM_005291 GPR17 G protein-coupled G-protein coupled receptor, 2820 6788 receptor 17 Transmembrane, Glycoprotein, Alternative splicing, Receptor NM_005327 HADHSC L-3-hydroxyacyl- Fatty acid metabolism, 2821 6789 Coenzyme A Oxidoreductase, NAD, dehydrogenase, Mitochondrion, Transit peptide, 3D- short chain structure NM_005335 HCLS1 hematopoietic cell- Repeat, SH3 domain, 2822 6790 specific Lyn Phosphorylation substrate 1 NM_005340 HINT1 histidine triad Hydrolase, Acetylation, 3D-structure 2823 6791 nucleotide binding protein 1 NM_005345 HSPA1A heat shock 70 kDa ATP-binding, Chaperone, Heat 2824 6792 protein 1A shock, Multigene family, 3D- structure NM_005346 HSPA1B heat shock 70 kDa ATP-binding, Chaperone, Heat 2825 6793 protein 1B shock, Multigene family, 3D- structure NM_005357 LIPE lipase, hormone- Hydrolase, Lipid degradation, 2826 6794 sensitive Phosphorylation NM_005358 LMO7 LIM domain only 7 LIM domain, Metal-binding, Zinc, 2827 6795 Hypothetical protein, Zinc-finger NM_005360 MAF v-maf Proto-oncogene, Transcription 2828 6796 musculoaponeurotic regulation, DNA-binding, Nuclear fibrosarcoma protein, Alternative splicing, oncogene homolog Chromosomal translocation (avian) NM_005379 MYO1A myosin IA Myosin, Actin-binding, ATP-binding, 2829 6797 Calmodulin-binding, Repeat, Multigene family, Polymorphism, Disease mutation, Deafness NM_005381 NCL nucleolin Hypothetical protein 2830 6798 NM_005402 RALA v-ral simian GTP-binding, Prenylation, 2831 6799 leukemia viral Lipoprotein oncogene homolog A (ras related) NM_005428 VAV1 vav 1 oncogene Hypothetical protein, SH3 domain, 2832 6800 Proto-oncogene, Phorbol-ester binding, Zinc, SH2 domain, Guanine- nucleotide releasing factor, Repeat, Phosphorylation NM_005433 YES1 v-yes-1 Yamaguchi Proto-oncogene, Tyrosine-protein 2833 6801 sarcoma viral kinase, Phosphorylation, oncogene homolog 1 Transferase, ATP-binding, Myristate, SH3 domain, SH2 domain, Lipoprotein NM_005436 D10S170 DNA segment on Proto-oncogene, Chromosomal 2834 6802 chromosome 10 translocation, SH3-binding, Repeat (unique) 170 NM_005439 MLF2 myeloid leukemia Nuclear protein 2835 6803 factor 2 NM_005441 CHAF1B chromatin assembly DNA replication, DNA repair, Cell 2836 6804 factor 1, subunit B cycle, Nuclear protein, (p60) Phosphorylation, Repeat, WD repeat NM_005451 ENIGMA enigma (LIM domain LIM domain, Metal-binding, Zinc 2837 6805 protein) NM_005463 HNRPDL heterogeneous Nucleocapsid, Ribonucleoprotein 2838 6806 nuclear ribonucleoprotein D- like NM_005466 MED6 mediator of RNA Transcription regulation, Activator, 2839 6807 polymerase II Receptor, Nuclear protein transcription, subunit 6 homolog (yeast) NM_005472 KCNE3 potassium voltage- Transport, Ion transport, Ionic 2840 6808 gated channel, lsk- channel, Voltage-gated channel, related family, Potassium channel, Potassium, member 3 Potassium transport, Transmembrane, Glycoprotein, Disease mutation NM_005479 FRAT1 frequently Wnt signaling pathway, Proto- 2841 6809 rearranged in oncogene, 3D-structure advanced T-cell lymphomas NM_005480 TROAP trophinin associated Cell adhesion, Repeat, Cytoskeleton 2842 6810 protein (tastin) NM_005488 TOM1 target of myb1 Hypothetical protein, Transport, 2843 6811 (chicken) Protein transport, Membrane, 3D- structure NM_005490 SH2D3A SH2 domain Hypothetical protein 2844 6812 containing 3A NM_005498 AP1M2 adaptor-related Golgi stack, Protein transport, 2845 6813 protein complex 1, Transport, Coated pits, Endocytosis, mu 2 subunit Phosphorylation, Alternative splicing NM_005499 UBA2 SUMO-1 activating Cyclin, Hypothetical protein 2846 6814 enzyme subunit 2 NM_005501 ITGA3 integrin, alpha 3 Integrin, Cell adhesion, Receptor, 2847 6815 (antigen CD49C, Glycoprotein, Transmembrane, alpha 3 subunit of Signal, Phosphorylation, Repeat, VLA-3 receptor) Alternative splicing, Calcium NM_005504 BCAT1 branched chain Transferase, Aminotransferase, 2848 6816 aminotransferase 1, Branched-chain amino acid cytosolic biosynthesis, Pyridoxal phosphate, Hypothetical protein NM_005505 SCARB1 scavenger receptor Transcription regulation, Nuclear 2849 6817 class B, member 1 protein, Receptor, Transmembrane, Glycoprotein, Polymorphism, Alternative splicing NM_005507 CFL1 cofilin 1 (non- Nuclear protein, Actin-binding, 2850 6818 muscle) Cytoskeleton, Phosphorylation NM_005510 DOM3Z dom-3 homolog Z Transferase, Serine/threonine- 2851 6819 (C. elegans) protein kinase, ATP-binding, Manganese, Nuclear protein, Alternative splicing NM_005512 GARP glycoprotein A Glycoprotein, Leucine-rich repeat, 2852 6820 repetitions Repeat, Transmembrane, Signal predominant NM_005514 HLA-B major Glycoprotein, MHC I, Signal, 2853 6821 histocompatibility Transmembrane, Polymorphism, 3D- complex, class I, B structure, Alternative splicing, Hypothetical protein, Sulfation NM_005516 HLA-E major Glycoprotein, Transmembrane, 2854 6822 histocompatibility Hypothetical protein, MHC I, Signal, complex, class I, E Polymorphism, 3D-structure NM_005517 HMGN2 high-mobility group Hypothetical protein, Microtubule, 2855 6823 nucleosomal binding GTP-binding, Multigene family, domain 2 Nuclear protein, DNA-binding, Polymorphism NM_005527 HSPA1L heat shock 70 kDa ATP-binding, Multigene family, 2856 6824 protein 1-like Polymorphism NM_005534 IFNGR2 interferon gamma Receptor, Transmembrane, 2857 6825 receptor 2 (interferon Glycoprotein, Signal, Repeat gamma transducer 1) NM_005541 INPP5D inositol 2858 6826 polyphosphate-5- phosphatase, 145 kDa NM_005548 KARS lysyl-tRNA Aminoacyl-tRNA synthetase, Protein 2859 6827 synthetase biosynthesis, Ligase, ATP-binding, Polymorphism NM_005564 LCN2 lipocalin 2 Glycoprotein, Lipocalin, Signal, 3D- 2860 6828 (oncogene 24p3) structure, Pyrrolidone carboxylic acid NM_005565 LCP2 lymphocyte cytosolic SH2 domain, Phosphorylation 2861 6829 protein 2 (SH2 domain containing leukocyte protein of 76 kDa) NM_005574 LMO2 LIM domain only 2 Proto-oncogene, Repeat, LIM 2862 6830 (rhombotin-like 1) domain, Metal-binding, Zinc, Nuclear protein, Alternative splicing, Chromosomal translocation NM_005578 LPP LIM domain LIM domain, Metal-binding, Zinc 2863 6831 containing preferred translocation partner in lipoma NM_005586 MDFI MyoD family inhibitor Differentiation 2864 6832 NM_005590 MRE11A MRE11 meiotic DNA repair, Hydrolase, Nuclease, 2865 6833 recombination 11 Endonuclease, Exonuclease, homolog A (S. cerevisiae) Nuclear protein, Manganese, Meiosis, Alternative splicing, Disease mutation, Polymorphism, Hypothetical protein NM_005598 NHLH1 nescient helix loop DNA-binding, Transcription 2866 6834 helix 1 regulation, Differentiation NM_005601 NKG7 natural killer cell Transmembrane 2867 6835 group 7 sequence NM_005605 PPP3CC protein phosphatase Hypothetical protein, Hydrolase, 2868 6836 3 (formerly 2B), Iron, Manganese, Calmodulin- catalytic subunit, binding, Metal-binding, Zinc, gamma isoform Multigene family (calcineurin A gamma) NM_005607 PTK2 PTK2 protein Hypothetical protein, ATP-binding, 2869 6837 tyrosine kinase 2 Transferase, Kinase, Tyrosine- protein kinase, Phosphorylation, Alternative splicing, 3D-structure NM_005608 PTPRCAP protein tyrosine Transmembrane, Phosphorylation 2870 6838 phosphatase, receptor type, C- associated protein NM_005611 RBL2 retinoblastoma-like 2 ATP-binding, Kinase, 2871 6839 (p130) Serine/threonine-protein kinase, Transferase, Transcription regulation, DNA-binding, Nuclear protein, Cell cycle, Phosphorylation, Anti-oncogene NM_005620 S100A11 S100 calcium Calcium-binding 2872 6840 binding protein A11 (calgizzarin) NM_005621 S100A12 S100 calcium Calcium-binding, Zinc, Metal- 2873 6841 binding protein A12 binding, Antibiotic, Fungicide, 3D- (calgranulin C) structure NM_005623 CCL8 chemokine (C—C Cytokine, Chemotaxis, Signal, 2874 6842 motif) ligand 8 Heparin-binding, Inflammatory response, Polymorphism, Pyrrolidone carboxylic acid, 3D- structure NM_005625 SDCBP syndecan binding Cytoskeleton, Membrane, 2875 6843 protein (syntenin) Endoplasmic reticulum, Nuclear protein, Phosphorylation, Repeat, Polymorphism NM_005646 TARBP1 TAR (HIV) RNA 2876 6844 binding protein 1 NM_005647 TBL1X transducin (beta)-like Repeat, WD repeat 2877 6845 1X-linked NM_005654 NR2F1 nuclear receptor Receptor, Transcription regulation, 2878 6846 subfamily 2, group F, DNA-binding, Nuclear protein, Zinc- member 1 finger, Activator NM_005658 TRAF1 TNF receptor- Apoptosis, Coiled coil 2879 6847 associated factor 1 NM_005687 FRSB phenylalanyl-tRNA Aminoacyl-tRNA synthetase, Protein 2880 6848 synthetase beta- biosynthesis, Ligase, ATP-binding subunit NM_005690 DNM1L dynamin 1-like Hypothetical protein 2881 6849 NM_005697 SCAMP2 secretory carrier Transmembrane, Transport, Protein 2882 6850 membrane protein 2 transport, Multigene family NM_005704 PTPRU protein tyrosine Glycoprotein, Hydrolase, Receptor, 2883 6851 phosphatase, Repeat, Signal, Transmembrane, receptor type, U Immunoglobulin domain NM_005710 PQBP1 polyglutamine Nuclear protein 2884 6852 binding protein 1 NM_005713 COL4A3BP collagen, type IV, Transferase, Kinase, 2885 6853 alpha 3 Serine/threonine-protein kinase, (Goodpasture Coiled coil, Alternative splicing antigen) binding protein NM_005716 RGS19IP1 regulator of G- 2886 6854 protein signalling 19 interacting protein 1 NM_005717 ARPC5 actin related protein Cytoskeleton 2887 6855 2/3 complex, subunit 5, 16 kDa NM_005720 ARPC1B actin related protein Hypothetical protein, Repeat, WD 2888 6856 2/3 complex, subunit repeat, Polymorphism 1B, 41 kDa NM_005724 TSPAN-3 transmembrane 4 Glycoprotein, Transmembrane 2889 6857 superfamily member 8 NM_005725 TSPAN-2 tetraspan 2 Glycoprotein, Transmembrane 2890 6858 NM_005730 OS4 CTD (carboxy- Hypothetical protein, Nuclear protein 2891 6859 terminal domain, RNA polymerase II, polypeptide A) small phosphatase 2 NM_005731 ARPC2 actin related protein Cytoskeleton 2892 6860 2/3 complex, subunit 2, 34 kDa NM_005732 RAD50 RAD50 homolog (S. cerevisiae) 2893 6861 NM_005733 KIF20A kinesin family Motor protein, Microtubule, ATP- 2894 6862 member 20A binding, Coiled coil, Golgi stack, Protein transport, Transport NM_005736 ACTR1A ARP1 actin-related Structural protein, Cytoskeleton, 2895 6863 protein 1 homolog A, Multigene family centractin alpha (yeast) NM_005737 ARL7 ADP-ribosylation GTP-binding, Multigene family, 2896 6864 factor-like 7 Nuclear protein NM_005741 ZNF263 zinc finger protein Transcription regulation, Zinc-finger, 2897 6865 263 Metal-binding, Nuclear protein, DNA- binding, Repeat, Repressor NM_005759 ABI-2 abl-interactor 2 Kinase, SH3 domain 2898 6866 NM_005761 PLXNC1 plexin C1 2899 6867 NM_005762 TRIM28 tripartite motif- Transcription regulation, Repressor, 2900 6868 containing 28 Nuclear protein, Zinc-finger, Repeat, 3D-structure NM_005770 SERF2 small EDRK-rich Hypothetical protein 2901 6869 factor 2 NM_005771 RDHL dehydrogenase/reductase Oxidoreductase 2902 6870 (SDR family) member 9 NM_005772 PLAA RNA terminal Repeat, WD repeat, Hypothetical 2903 6871 phosphate cyclase- protein, Nuclear protein like 1 NM_005773 ZNF256 zinc finger protein Transcription regulation, DNA- 2904 6872 256 binding, Zinc-finger, Metal-binding, Nuclear protein, Repeat NM_005787 NOT56L asparagine-linked Hypothetical protein, Transferase, 2905 6873 glycosylation 3 Glycosyltransferase, homolog (yeast, Transmembrane, Endoplasmic alpha-1,3- reticulum, Disease mutation mannosyltransferase) NM_005797 EVA1 epithelial V-like Cell adhesion, Immunoglobulin 2906 6874 antigen 1 domain, Transmembrane, Glycoprotein, Signal NM_005803 FLOT1 flotillin 1 Membrane 2907 6875 NM_005805 PSMD14 proteasome Proteasome 2908 6876 (prosome, macropain) 26S subunit, non- ATPase, 14 NM_005811 GDF11 growth differentiation Growth factor, Cytokine, 2909 6877 factor 11 Glycoprotein, Signal NM_005826 HNRPR heterogeneous Nucleocapsid, Ribonucleoprotein, 2910 6878 nuclear Nuclear protein, RNA-binding, ribonucleoprotein R Repeat NM_005833 RAB9P40 Rab9 effector p40 2911 6879 NM_005834 TIMM17B translocase of inner Transport, Protein transport, 2912 6880 mitochondrial Translocation, Mitochondrion, Inner membrane 17 membrane, Transmembrane homolog B (yeast) NM_005836 UK114 translational inhibitor Nuclear protein 2913 6881 protein p14.5 NM_005845 ABCC4 ATP-binding ATP-binding, Glycoprotein, 2914 6882 cassette, sub-family Transmembrane, Transport, Repeat C (CFTR/MRP), member 4 NM_005849 IGSF6 immunoglobulin Signal, Hypothetical protein 2915 6883 superfamily, member 6 NM_005855 RAMP1 receptor (calcitonin) Signal, Transmembrane, Transport, 2916 6884 activity modifying Receptor protein 1 NM_005860 FSTL3 follistatin-like 3 Glycoprotein, Repeat, Signal, 2917 6885 (secreted Chromosomal translocation, Proto- glycoprotein) oncogene NM_005862 STAG1 stromal antigen 1 Mitosis, Cell cycle, Chromosome 2918 6886 partition, Nuclear protein, Phosphorylation NM_005863 NET1 neuroepithelial cell 2919 6887 transforming gene 1 NM_005865 PRSS16 protease, serine, 16 Hydrolase, Serine protease, Signal 2920 6888 (thymus) NM_005866 SR-BP1 opioid receptor, Hypothetical protein, Receptor 2921 6889 sigma 1 NM_005873 RGS19 regulator of G- Signal transduction inhibitor, 2922 6890 protein signalling 19 Membrane, Lipoprotein, Palmitate, Phosphorylation, Autophagy, 3D- structure NM_005874 LILRB2 leukocyte Receptor, Repeat, Signal, 2923 6891 immunoglobulin-like Transmembrane, Immune response, receptor, subfamily Immunoglobulin domain, B (with TM and ITIM Phosphorylation, Glycoprotein, domains), member 2 Antigen, Multigene family, Alternative splicing, Polymorphism NM_005884 PAK4 p21(CDKN1A)- Hypothetical protein, ATP-binding, 2924 6892 activated kinase 4 Transferase, Serine/threonine- protein kinase, Phosphorylation, Alternative splicing NM_005886 KATNB1 katanin p80 (WD Repeat, WD repeat 2925 6893 repeat containing) subunit B 1 NM_005888 SLC25A3 solute carrier family Mitochondrion, Inner membrane, 2926 6894 25 (mitochondrial Repeat, Transit peptide, carrier; phosphate Transmembrane, Transport, carrier), member 3 Symport, Alternative splicing, Hypothetical protein NM_005891 ACAT2 acetyl-Coenzyme A Chaperone, ATP-binding, Multigene 2927 6895 acetyltransferase 2 family, Transferase (acetoacetyl Coenzyme A thiolase) NM_005892 FMNL formin-like 1 Hypothetical protein 2928 6896 NM_005898 M11S1 membrane GPI-anchor 2929 6897 component, chromosome 11, surface marker 1 NM_005900 MADH1 MAD, mothers Transcription regulation, 2930 6898 against Phosphorylation, Multigene family, decapentaplegic 3D-structure homolog 1 (Drosophila) NM_005902 MADH3 MAD, mothers Transcription regulation, 2931 6899 against Phosphorylation, Multigene family, decapentaplegic 3D-structure homolog 3 (Drosophila) NM_005917 MDH1 malate Oxidoreductase, Tricarboxylic acid 2932 6900 dehydrogenase 1, cycle, NAD NAD (soluble) NM_005931 MICB MHC class I Glycoprotein, Transmembrane, MHC 2933 6901 polypeptide-related sequence B NM_005932 MIPEP mitochondrial Hydrolase, Metalloprotease, Zinc, 2934 6902 intermediate Transit peptide, Mitochondrion, peptidase Magnesium, Manganese, Calcium, Cobalt, Iron NM_005935 MLLT2 myeloid/lymphoid or Alternative splicing, Chromosomal 2935 6903 mixed-lineage translocation, Proto-oncogene, DNA- leukemia (trithorax binding, Bromodomain, Nuclear homolog, protein, Zinc-finger, Metal-binding, Drosophila); Transcription regulation, Repeat, translocated to, 2 Hypothetical protein, Serine/threonine-protein kinase, Transferase, ATP-binding, Tran NM_005950 MT1G metallothionein 1G Metal-binding, Metal-thiolate cluster, 2936 6904 Zinc, Copper, Cadmium, Acetylation NM_005952 MT1X metallothionein 1X Hypothetical protein, Metal-binding, 2937 6905 Metal-thiolate cluster, Zinc, Copper, Cadmium, Acetylation NM_005953 MT2A metallothionein 2A Metal-binding, Metal-thiolate cluster, 2938 6906 Zinc, Acetylation, 3D-structure NM_005954 MT3 metallothionein 3 Metal-binding, Metal-thiolate cluster, 2939 6907 (growth inhibitory Zinc, Copper, Acetylation factor (neurotrophic)) NM_005955 MTF1 metal-regulatory Hypothetical protein, Metal-binding, 2940 6908 transcription factor 1 Zinc, Zinc-finger NM_005965 MYLK myosin, light Immunoglobulin domain, Kinase, 2941 6909 polypeptide kinase ATP-binding, Repeat, Serine/threonine-protein kinase, Transferase, Calmodulin-binding, Phosphorylation, Alternative initiation, Alternative splicing NM_005969 NAP1L4 nucleosome Nuclear protein 2942 6910 assembly protein 1- like 4 NM_005975 PTK6 PTK6 protein Transferase, Tyrosine-protein 2943 6911 tyrosine kinase 6 kinase, ATP-binding, SH2 domain, SH3 domain, Phosphorylation NM_005979 S100A13 S100 calcium Calcium-binding 2944 6912 binding protein A13 NM_005980 S100P S100 calcium Calcium-binding, Placenta, 3D- 2945 6913 binding protein P structure NM_005988 SPRR2A small proline-rich Keratinocyte, Repeat, Multigene 2946 6914 protein 2A family NM_005990 STK10 serine/threonine Kinase, Transferase, 2947 6915 kinase 10 Serine/threonine-protein kinase, ATP-binding, Phosphorylation, Coiled coil NM_005998 CCT3 chaperonin Chaperone, ATP-binding, Multigene 2948 6916 containing TCP1, family, Hypothetical protein subunit 3 (gamma) NM_006002 UCHL3 ubiquitin carboxyl- Ubl conjugation pathway, Hydrolase, 2949 6917 terminal esterase L3 Thiol protease, Multigene family, 3D- (ubiquitin structure thiolesterase) NM_006018 HM74 putative chemokine G-protein coupled receptor, 2950 6918 receptor Transmembrane NM_006019 TCIRG1 T-cell, immune Hydrogen ion transport, 2951 6919 regulator 1, ATPase, Transmembrane, Glycoprotein, H+ transporting, Alternative splicing, Hypothetical lysosomal V0 protein protein a isoform 3 NM_006022 TSC22 transforming growth Hypothetical protein, Transcription 2952 6920 factor beta- regulation, Repressor, Nuclear stimulated protein protein TSC-22 NM_006027 EXO1 exonuclease 1 Exonuclease, Hypothetical protein 2953 6921 NM_006029 PNMA1 paraneoplastic Antigen, Tumor antigen, Nuclear 2954 6922 antigen MA1 protein NM_006031 PCNT2 pericentrin 2 Coiled coil, Hypothetical protein 2955 6923 (kendrin) NM_006034 TP53I11 tumor protein p53 Hypothetical protein 2956 6924 inducible protein 11 NM_006053 TCIRG1 T-cell, immune Hydrogen ion transport, 2957 6925 regulator 1, ATPase, Transmembrane, Glycoprotein, H+ transporting, Alternative splicing, Hypothetical lysosomal V0 protein protein a isoform 3 NM_006054 RTN3 reticulon 3 Hypothetical protein, 2958 6926 Transmembrane, Endoplasmic reticulum NM_006055 LANCL1 LanC lantibiotic Transmembrane 2959 6927 synthetase component C-like 1 (bacterial) NM_006060 ZNFN1A1 zinc finger protein, Transcription regulation, Activator, 2960 6928 subfamily 1A, 1 Zinc-finger, Metal-binding, DNA- (lkaros) binding, Nuclear protein, Repeat, Alternative splicing NM_006061 SGP28 cysteine-rich Glycoprotein, Signal, Multigene 2961 6929 secretory protein 3 family, Polymorphism NM_006069 MRVI1 murine retrovirus 2962 6930 integration site 1 homolog NM_006070 TFG TRK-fused gene Hypothetical protein, Ligase, GMP 2963 6931 biosynthesis, Purine biosynthesis, ATP-binding, Glutamine amidotransferase NM_006079 CITED2 Cbp/p300-interacting Transcription regulation, Nuclear 2964 6932 transactivator, with protein, Alternative splicing Glu/Asp-rich carboxy-terminal domain, 2 NM_006088 TUBB2 tubulin, beta, 2 Microtubule, GTP-binding, Multigene 2965 6933 family, Hypothetical protein NM_006093 PRG3 proteoglycan 3 2966 6934 NM_006097 MYL9 myosin, light Myosin, Calcium-binding, Muscle 2967 6935 polypeptide 9, protein, Phosphorylation, regulatory Acetylation, Multigene family NM_006103 WFDC2 WAP four-disulfide Serine protease inhibitor, Repeat, 2968 6936 core domain 2 Signal, Glycoprotein, Alternative splicing NM_006107 LUC7A acid-inducible Phosphorylation, Hypothetical 2969 6937 phosphoprotein protein NM_006109 SKB1 SKB1 homolog (S. pombe) Transferase, Methyltransferase, 2970 6938 Alternative splicing NM_006111 ACAA2 acetyl-Coenzyme A Acyltransferase, Transferase, Fatty 2971 6939 acyltransferase 2 acid metabolism, Mitochondrion, (mitochondrial 3- Transit peptide oxoacyl-Coenzyme A thiolase) NM_006113 VAV3 vav 3 oncogene SH3 domain, Phorbol-ester binding, 2972 6940 Zinc, SH2 domain, Repeat, Guanine- nucleotide releasing factor, Alternative splicing NM_006115 PRAME preferentially Antigen 2973 6941 expressed antigen in melanoma NM_006117 PECI peroxisomal D3,D2- Isomerase, Hypothetical protein, 2974 6942 enoyl-CoA Peroxisome isomerase NM_006135 CAPZA1 capping protein Actin-binding, Multigene family, 3D- 2975 6943 (actin filament) structure, Actin capping muscle Z-line, alpha 1 NM_006138 MS4A3 membrane-spanning Receptor, Transmembrane, 2976 6944 4-domains, Alternative splicing, Multigene family subfamily A, member 3 (hematopoietic cell- specific) NM_006139 CD28 CD28 antigen (Tp44) Immunoglobulin domain, T-cell, 2977 6945 Glycoprotein, Signal, Transmembrane, Alternative splicing NM_006140 CSF2RA colony stimulating Receptor, Transmembrane, 2978 6946 factor 2 receptor, Glycoprotein, Signal, Alternative alpha, low-affinity splicing (granulocyte- macrophage) NM_006142 SFN stratifin Multigene family 2979 6947 NM_006144 GZMA granzyme A Hydrolase, Serine protease, 2980 6948 (granzyme 1, Zymogen, Signal, T-cell, Cytolysis, cytotoxic T- Apoptosis, 3D-structure lymphocyte- associated serine esterase 3) NM_006145 DNAJB1 DnaJ (Hsp40) Heat shock, Chaperone, 3D- 2981 6949 homolog, subfamily structure B, member 1 NM_006147 IRF6 interferon regulatory Transcription regulation, DNA- 2982 6950 factor 6 binding, Nuclear protein, Polymorphism, Disease mutation NM_006148 LASP1 LIM and SH3 protein 1 LIM domain, Metal-binding, Zinc, 2983 6951 SH3 domain NM_006159 NELL2 NEL-like 2 (chicken) EGF-like domain, Glycoprotein, 2984 6952 Repeat, Signal NM_006161 NEUROG1 neurogenin 1 DNA-binding, Nuclear protein, 2985 6953 Transcription regulation, Activator, Neurogenesis, Developmental protein, Differentiation NM_006176 NRGN neurogranin (protein Calmodulin-binding, 2986 6954 kinase C substrate, Phosphorylation, Neurone RC3) NM_006185 NUMA1 nuclear mitotic Immunoglobulin domain, 2987 6955 apparatus protein 1 Glycoprotein, Signal, Alternative splicing, Hypothetical protein NM_006196 PCBP1 poly(rC) binding Nuclear protein, RNA-binding, 2988 6956 protein 1 Ribonucleoprotein, DNA-binding, Phosphorylation, Repeat NM_006202 PDE4A phosphodiesterase Hydrolase, cAMP, Alternative 2989 6957 4A, cAMP-specific splicing, Multigene family (phosphodiesterase E2 dunce homolog, Drosophila) NM_006205 PDE6H phosphodiesterase Hydrolase, cGMP, Vision 2990 6958 6H, cGMP-specific, cone, gamma NM_006214 PHYH phytanoyl-CoA Oxidoreductase, Peroxisome, 2991 6959 hydroxylase Vitamin C, Iron, Transit peptide, (Refsum disease) Disease mutation, Deafness, Retinitis pigmentosa, Hydrolase, cGMP, Vision, Prenylation, Lipoprotein, Membrane, Hypothetical protein, Collagen NM_006224 PITPN phosphotidylinositol Lipid-binding, Transport 2992 6960 transfer protein NM_006225 PLCD1 phospholipase C, Hydrolase, Lipid degradation, 2993 6961 delta 1 Transducer, Calcium-binding, Repeat NM_006238 PPARD peroxisome Receptor, Transcription regulation, 2994 6962 proliferative Activator, DNA-binding, Nuclear activated receptor, protein, Zinc-finger, Multigene family, delta 3D-structure, Metal-binding NM_006242 PPP1R3D protein phosphatase Hydrolase, Glycogen metabolism 2995 6963 1, regulatory subunit 3D NM_006243 PPP2R5A protein phosphatase Phosphorylation, Multigene family 2996 6964 2, regulatory subunit B (B56), alpha isoform NM_006244 PPP2R5B protein phosphatase Phosphorylation, Alternative splicing, 2997 6965 2, regulatory subunit Multigene family B (B56), beta isoform NM_006254 PRKCD protein kinase C, ATP-binding, Transferase, 2998 6966 delta Scrine/threonine-protein kinase, Phorbol-ester binding, Zinc, Repeat, Polymorphism, Phosphorylation, Membrane NM_006272 S100B S100 calcium Calcium-binding, Zinc, Metal- 2999 6967 binding protein, beta binding, 3D-structure (neural) NM_006284 TAF10 TAF10 RNA Transcription regulation, Nuclear 3000 6968 polymerase II, TATA protein, Polymorphism box binding protein (TBP)-associated factor, 30 kDa NM_006287 TFPI tissue factor Serine protease inhibitor, 3001 6969 pathway inhibitor Glycoprotein, Repeat, Blood (lipoprotein- coagulation, Signal, Alternative associated splicing, 3D-structure, Polymorphism coagulation inhibitor) NM_006289 TLN1 talin 1 Hypothetical protein, Structural 3002 6970 protein, Cytoskeleton NM_006290 TNFAIP3 tumor necrosis Apoptosis, DNA-binding, Zinc-finger, 3003 6971 factor, alpha-induced Repeat, Hypothetical protein protein 3 NM_006291 TNFAIP2 tumor necrosis Angiogenesis 3004 6972 factor, alpha-induced protein 2 NM_006304 DSS1 split hand/foot Polymorphism, 3D-structure 3005 6973 malformation (ectrodactyly) type 1 NM_006310 NPEPPS aminopeptidase Hydrolase, Metalloprotease, 3006 6974 puromycin sensitive Aminopeptidase, Zinc, Nuclear protein NM_006314 CNK1 connector enhancer Hypothetical protein, Kinase 3007 6975 of KSR-like (Drosophila kinase suppressor of ras) NM_006317 BASP1 brain abundant, Membrane, Myristate, Neurone, 3008 6976 membrane attached Lipoprotein signal protein 1 NM_006319 CDIPT CDP-diacylglycerol- Transferase, Phospholipid 3009 6977 inositol 3- biosynthesis, Transmembrane, phosphatidyltransferase Magnesium, Manganese (phosphatidylinositol synthase) NM_006321 ARIH2 ariadne homolog 2 Ubl conjugation pathway, Nuclear 3010 6978 (Drosophila) protein, Coiled coil, Zinc-finger, Repeat NM_006323 SEC24B SEC24 related gene Transport, Protein transport, Golgi 3011 6979 family, member B (S. cerevisiae) stack, Endoplasmic reticulum, Multigene family NM_006324 CFDP1 craniofacial 3012 6980 development protein 1 NM_006327 TIMM23 translocase of inner Transport, Protein transport, 3013 6981 mitochondrial Translocation, Mitochondrion, Inner membrane 23 membrane, Outer membrane, homolog (yeast) Transmembrane NM_006342 TACC3 transforming, acidic Coiled coil 3014 6982 coiled-coil containing protein 3 NM_006344 HML2 C-type (calcium Lectin 3015 6983 dependent, carbohydrate- recognition domain) lectin, superfamily member 13 (macrophage- derived) NM_006345 C4orf1 solute carrier family Hypothetical protein 3016 6984 30 (zinc transporter), member 9 NM_006346 PIBF1 progesterone- 3017 6985 induced blocking factor 1 NM_006351 TIMM44 translocase of inner Mitochondrion, Inner membrane, 3018 6986 mitochondrial Transport, Protein transport, membrane 44 Translocation, Transit peptide, ATP- homolog (yeast) binding, Receptor NM_006353 HMGN4 high mobility group Nuclear protein, DNA-binding 3019 6987 nucleosomal binding domain 4 NM_006355 TRIM38 tripartite motif- Zinc-finger, Polymorphism 3020 6988 containing 38 NM_006360 GA17 dendritic cell protein Hypothetical protein 3021 6989 NM_006362 NXF1 nuclear RNA export Transport, mRNA transport, Nuclear 3022 6990 factor 1 protein, RNA-binding, Repeat, Leucine-rich repeat, Multigene family, 3D-structure NM_006367 CAP CAP, adenylate Membrane, Multigene family 3023 6991 cyclase-associated protein 1 (yeast) NM_006374 STK25 serine/threonine Hypothetical protein, ATP-binding, 3024 6992 kinase 25 (STE20 Transferase, Serine/threonine- homolog, yeast) protein kinase, Phosphorylation NM_006377 UNC13 unc-13 homolog B Phorbol-ester binding 3025 6993 (C. elegans) NM_006383 KIP2 DNA-dependent Calcium-binding, Repeat 3026 6994 protein kinase catalytic subunit- interacting protein 2 NM_006386 DDX17 DEAD (Asp-Glu-Ala- ATP-binding, RNA-binding, Helicase, 3027 6995 Asp) box polypeptide Nuclear protein 17 NM_006387 CHERP calcium homeostasis 3028 6996 endoplasmic reticulum protein NM_006389 HYOU1 hypoxia up-regulated 1 ATP-binding, Chaperone, 3029 6997 Endoplasmic reticulum, Signal, Glycoprotein NM_006395 GSA7 APG7 autophagy 7- Hypothetical protein 3030 6998 like (S. cerevisiae) NM_006399 BATF basic leucine zipper Transcription regulation, DNA- 3031 6999 transcription factor, binding, Repressor, Phosphorylation, ATF-like Nuclear protein NM_006403 NEDD9 neural precursor cell Phosphorylation, SH3 domain, Cell 3032 7000 expressed, adhesion, Growth regulation, developmentally Cytoskeleton, Mitosis, Nuclear down-regulated 9 protein NM_006404 PROCR protein C receptor, Blood coagulation, Receptor, Signal, 3033 7001 endothelial (EPCR) Transmembrane, Glycoprotein, Antigen, Polymorphism, 3D-structure NM_006405 TM9SF1 transmembrane 9 Hypothetical protein, Plasmid, 3034 7002 superfamily member 1 Signal, Transmembrane, Glycoprotein NM_006406 PRDX4 peroxiredoxin 4 Antioxidant, Peroxidase, 3035 7003 Oxidoreductase, Redox-active center NM_006421 BIG1 brefeldin A-inhibited Guanine-nucleotide releasing factor 3036 7004 guanine nucleotide- exchange protein 1 NM_006429 CCT7 chaperonin Chaperone, ATP-binding, Multigene 3037 7005 containing TCP1, family subunit 7 (eta) NM_006430 CCT4 chaperonin Chaperone, ATP-binding, Multigene 3038 7006 containing TCP1, family, Hypothetical protein subunit 4 (delta) NM_006431 CCT2 chaperonin ATP-binding, Chaperone, Multigene 3039 7007 containing TCP1, family subunit 2 (beta) NM_006433 GNLY granulysin Antibiotic, Fungicide, Signal, T-cell, 3040 7008 Alternative splicing, 3D-structure NM_006435 IFITM2 interferon induced Interferon induction, 3041 7009 transmembrane Transmembrane, Polymorphism protein 2 (1-8D) NM_006441 MTHFS 5,10- Ligase, Folate-binding, Acetylation, 3042 7010 methenyltetrahydrofolate Magnesium, Hypothetical protein synthetase (5- formyltetrahydrofolate cyclo-ligase) NM_006451 PAIP1 poly(A) binding Hypothetical protein 3043 7011 protein interacting protein 1 NM_006452 PAICS phosphoribosylaminoimidazole Multifunctional enzyme, Purine 3044 7012 carboxylase, biosynthesis, Ligase, Lyase, phosphoribosylaminoimidazole Decarboxylase succinocarboxamide synthetase NM_006455 SC65 synaptonemal Nuclear protein, Antigen 3045 7013 complex protein SC65 NM_006456 STHM sialyltransferase Transferase, Glycosyltransferase, 3046 7014 Glycoprotein, Transmembrane, Signal-anchor, Golgi stack NM_006461 SPAG5 sperm associated Hypothetical protein 3047 7015 antigen 5 NM_006465 DRIL2 dead ringer 3048 7016 (Drosophila)-like 2 (bright and dead ringer) NM_006469 IVNS1ABP influenza virus NS1A Hypothetical protein 3049 7017 binding protein NM_006471 MLC-B myosin regulatory Myosin, Calcium-binding, Muscle 3050 7018 light chain MRCL3 protein, Phosphorylation, Acetylation, Multigene family NM_006472 TXNIP thioredoxin 3051 7019 interacting protein NM_006477 RRP22 RAS-related on GTP-binding, Prenylation, 3052 7020 chromosome 22 Lipoprotein NM_006480 RGS14 regulator of G- Repeat, Thiol protease inhibitor, 3053 7021 protein signalling 14 Alternative splicing, Phosphorylation, Signal transduction inhibitor NM_006495 EVI2B ecotropic viral Proto-oncogene, Transmembrane, 3054 7022 integration site 2B Glycoprotein, Signal NM_006542 SPHAR S-phase response 3055 7023 (cyclin-related) NM_006545 NPR2L homologous to yeast Hypothetical protein 3056 7024 nitrogen permease (candidate tumor suppressor) NM_006560 CUGBP1 CUG triplet repeat, Hypothetical protein, mRNA 3057 7025 RNA binding protein 1 processing, RNA-binding, Repeat, Nuclear protein, Alternative splicing NM_006567 FARS1 phenylalanine-tRNA Aminoacyl-tRNA synthetase 3058 7026 synthetase 1 (mitochondrial) NM_006568 CGR19 cell growth regulator Metal-binding, Zinc, Zinc-finger 3059 7027 with ring finger domain 1 NM_006575 MAP4K5 mitogen-activated ATP-binding, Kinase, Transferase, 3060 7028 protein kinase Tyrosine-protein kinase, kinase kinase kinase 5 Serine/threonine-protein kinase NM_006578 GNB5 guanine nucleotide Repeat, WD repeat, Transducer, 3061 7029 binding protein (G Alternative splicing, Multigene family, protein), beta 5 Hypothetical protein NM_006589 C1orf2 chromosome 1 open Hypothetical protein 3062 7030 reading frame 2 NM_006598 SLC12A7 solute carrier family Transport, Ion transport, Symport, 3063 7031 12 Potassium, Potassium transport, (potassium/chloride Transmembrane, Alternative splicing transporters), member 7 NM_006636 MTHFD2 methylene Multifunctional enzyme, One-carbon 3064 7032 tetrahydrofolate metabolism, Oxidoreductase, NAD, dehydrogenase Hydrolase, Mitochondrion, Transit (NAD+ dependent), peptide, Magnesium methenyltetrahydrofolate cyclohydrolase NM_006638 RNASEP1 ribonuclease P1 Hydrolase, Nuclear protein, tRNA 3065 7033 processing NM_006643 SDCCAG3 serologically defined Hypothetical protein 3066 7034 colon cancer antigen 3 NM_006644 HSPH1 heat shock ATP-binding, Heat shock, Multigene 3067 7035 105 kDa/110 kDa family, Alternative splicing protein 1 NM_006646 WASF3 WAS protein family, Actin-binding, Coiled coil 3068 7036 member 3 NM_006650 CPLX2 complexin 2 Neurotransmitter transport 3069 7037 NM_006660 CLPX ClpX caseinolytic Hypothetical protein, ATP-binding, 3070 7038 protease X homolog Chaperone, Mitochondrion, Transit (E. coli) peptide, Zinc-finger NM_006667 PGRMC1 progesterone Receptor, Steroid-binding, 3071 7039 receptor membrane Transmembrane, Microsome component 1 NM_006669 LILRB1 leukocyte Receptor, Repeat, Signal, 3072 7040 immunoglobulin-like Transmembrane, Immune response, receptor, subfamily Immunoglobulin domain, B (with TM and ITIM Phosphorylation, Glycoprotein, domains), member 1 Antigen, Multigene family, Alternative splicing, Polymorphism, 3D-structure NM_006676 USP20 ubiquitin specific Ubl conjugation pathway, Hydrolase, 3073 7041 protease 20 Thiol protease, Multigene family NM_006680 ME3 malic enzyme 3, Oxidoreductase, NADP, 3074 7042 NADP(+)- Mitochondrion, Transit peptide dependent, mitochondrial NM_006681 NMU neuromedin U Neuropeptide, Cleavage on pair of 3075 7043 basic residues, Amidation, Signal NM_006682 FGL2 fibrinogen-like 2 T-cell, Glycoprotein, Signal, 3076 7044 Polymorphism NM_006700 FLN29 FLN29 gene product 3077 7045 NM_006704 SUGT1 SGT1, suppressor of Ubl conjugation pathway, Repeat, 3078 7046 G2 allele of SKP1 TPR repeat (S. cerevisiae) NM_006705 GADD45G growth arrest and Differentiation, Apoptosis 3079 7047 DNA-damage- inducible, gamma NM_006706 TCERG1 transcription 3080 7048 elongation regulator 1 (CA150) NM_006708 GLO1 glyoxalase I Lyase, Zinc, Polymorphism, 3D- 3081 7049 structure NM_006710 COP9 COP9 signalosome 3082 7050 subunit 8 NM_006719 ABLIM1 actin binding LIM LIM domain, Metal-binding, Zinc, 3083 7051 protein 1 Hypothetical protein NM_006721 ADK adenosine kinase Transferase, Kinase, Purine salvage, 3084 7052 Magnesium, Alternative splicing, 3D- structure NM_006732 FOSB FBJ murine Nuclear protein, DNA-binding 3085 7053 osteosarcoma viral oncogene homolog B NM_006747 SIPA1 signal-induced GTPase activation, Coiled coil, 3086 7054 proliferation- Nuclear protein, Membrane associated gene 1 NM_006748 SLA Src-like-adaptor SH2 domain, SH3 domain, 3087 7055 Myristate, Phosphorylation, Lipoprotein NM_006750 SNTB2 syntrophin, beta 2 Actin-binding, Cytoskeleton, 3088 7056 (dystrophin- Microtubule, Calcium-binding, associated protein Calmodulin-binding, Membrane, A1, 59 kDa, basic Phosphorylation, Repeat, component 2) Polymorphism, Multigene family, Alternative splicing NM_006755 TALDO1 transaldolase 1 Hypothetical protein, Pentose shunt, 3089 7057 Transferase, Disease mutation, 3D- structure NM_006756 TCEA1 transcription Transcription regulation, Zinc-finger, 3090 7058 elongation factor A DNA-binding, Nuclear protein, (SII), 1 Alternative splicing, 3D-structure NM_006760 UPK2 uroplakin 2 Endoplasmic reticulum, Signal, 3091 7059 Transmembrane, Glycoprotein NM_006761 YWHAE tyrosine 3- Neurone, Acetylation, Multigene 3092 7060 monooxygenase/tryptophan family 5- monooxygenase activation protein, epsilon polypeptide NM_006762 LAPTM5 Lysosomal- Transmembrane, Lysosome 3093 7061 associated multispanning membrane protein-5 NM_006763 BTG2 BTG family, member 2 Signal 3094 7062 NM_006770 MARCO macrophage Collagen, Transmembrane, 3095 7063 receptor with Receptor, Glycoprotein, Signal- collagenous anchor structure NM_006783 GJB6 gap junction protein, Gap junction, Transmembrane, 3096 7064 beta 6 (connexin 30) Deafness, Disease mutation NM_006784 WDR3 WD repeat domain 3 WD repeat, Repeat, Nuclear protein 3097 7065 NM_006787 MAGED2 melanoma antigen, Antigen, Multigene family, 3098 7066 family D, 2 Polymorphism, Alternative splicing NM_006795 EHD1 EH-domain Calcium-binding, ATP-binding, 3099 7067 containing 1 Coiled coil NM_006801 KDELR1 KDEL (Lys-Asp-Glu- Endoplasmic reticulum, 3100 7068 Leu) endoplasmic Transmembrane, Protein transport, reticulum protein Receptor, Hypothetical protein, retention receptor 1 Transport NM_006805 HNRPA0 heterogeneous Nuclear protein, RNA-binding, 3101 7069 nuclear Ribonucleoprotein, Repeat, ribonucleoprotein A0 Methylation NM_006806 BTG3 BTG family, member 3 Alternative splicing 3102 7070 NM_006810 PDIR for protein disulfide Isomerase, Redox-active center, 3103 7071 isomerase-related Endoplasmic reticulum, Repeat, Signal NM_006812 OS-9 amplified in Hypothetical protein, Signal, 3104 7072 osteosarcoma Alternative splicing, Polymorphism NM_006818 AF1Q ALL1-fused gene Proto-oncogene, Chromosomal 3105 7073 from chromosome translocation 1q NM_006823 PKIA protein kinase Protein kinase inhibitor, 3D-structure 3106 7074 (cAMP-dependent, catalytic) inhibitor alpha NM_006824 EBNA1BP2 EBNA1 binding Ribosome biogenesis, Nuclear 3107 7075 protein 2 protein, Coiled coil NM_006825 CKAP4 cytoskeleton- Hypothetical protein 3108 7076 associated protein 4 NM_006826 YWHAQ tyrosine 3- Transcription regulation, Repressor, 3109 7077 monooxygenase/tryptophan Activator, Nuclear protein, Zinc- 5- finger, Metal-binding, DNA-binding, monooxygenase Repeat, 3D-structure, Tight junction, activation protein, Immunoglobulin domain, theta polypeptide Glycoprotein, Transmembrane, Signal, Neurone, Phosphorylation, Multigene family NM_006827 TMP21 transmembrane Transport, Protein transport, 3110 7078 trafficking protein Transmembrane, Signal, Glycoprotein, Golgi stack, Polymorphism NM_006838 METAP2 methionyl Hydrolase, Aminopeptidase, Cobalt, 3111 7079 aminopeptidase 2 3D-structure, Hypothetical protein NM_006840 LILRB5 leukocyte Receptor, Repeat, Signal, 3112 7080 immunoglobulin-like Transmembrane, Immune response, receptor, subfamily Immunoglobulin domain, B (with TM and ITIM Phosphorylation, Glycoprotein, domains), member 2 Antigen, Multigene family, Alternative splicing NM_006863 LILRA1 leukocyte Immune response, Receptor, 3113 7081 immunoglobulin-like Repeat, Signal, Transmembrane, receptor, subfamily Immunoglobulin domain, B (with TM and ITIM Glycoprotein, Antigen, Alternative domains), member 1 splicing, Multigene family NM_006864 LILRB3 leukocyte Receptor, Repeat, Signal, 3114 7082 immunoglobulin-like Transmembrane, Immune response, receptor, subfamily Immunoglobulin domain, B (with TM and ITIM Phosphorylation, Glycoprotein, domains), member 3 Antigen, Multigene family, Alternative splicing, Polymorphism NM_006865 LILRA3 leukocyte Receptor, Repeat, Signal, Immune 3115 7083 immunoglobulin-like response, Immunoglobulin domain, receptor, subfamily Glycoprotein, Antigen, Multigene A (without TM family, Polymorphism domain), member 3 NM_006866 LILRA2 leukocyte Immune response, Receptor, 3116 7084 immunoglobulin-like Repeat, Signal, Transmembrane, receptor, subfamily Immunoglobulin domain, B (with TM and ITIM Glycoprotein, Antigen, Alternative domains), member 1 splicing, Polymorphism, Multigene family NM_006868 RAB31 RAB31, member GTP-binding, Lipoprotein, 3117 7085 RAS oncogene Prenylation family NM_006869 CENTA1 centaurin, alpha 1 3118 7086 NM_006876 B3GNT6 UDP- Transferase, Glycosyltransferase, 3119 7087 GlcNAc:betaGal Transmembrane, Signal-anchor, beta-1,3-N- Glycoprotein, Golgi stack acetylglucosaminyltransferase 6 NM_006890 CEACAM7 carcinoembryonic Immunoglobulin domain, Antigen, 3120 7088 antigen-related cell Membrane, Signal, Glycoprotein, adhesion molecule 7 Lipoprotein, GPI-anchor, Repeat, Alternative splicing NM_006892 DNMT3B DNA (cytosine-5-)- Transferase, Methyltransferase, 3121 7089 methyltransferase 3 Zinc-finger, Zinc, Metal-binding, beta Nuclear protein, Ubl conjugation, Alternative splicing, Disease mutation NM_006913 RNF5 ring finger protein 5 Hypothetical protein 3122 7090 NM_006923 SDF2 stromal cell-derived Signal, Repeat 3123 7091 factor 2 NM_006930 SKP1A S-phase kinase- Ubl conjugation pathway, Alternative 3124 7092 associated protein splicing, 3D-structure 1A (p19A) NM_006931 SLC2A3 solute carrier family Sugar transport, Transmembrane, 3125 7093 2 (facilitated glucose Transport, Glycoprotein, Multigene transporter), family member 3 NM_006932 SMTN smoothelin Structural protein, Alternative 3126 7094 splicing NM_006936 SMT3H1 SMT3 suppressor of Ubl conjugation pathway 3127 7095 mif two 3 homolog 1 (yeast) NM_006938 SNRPD1 small nuclear Nuclear protein, Ribonucleoprotein, 3128 7096 ribonucleoprotein D1 mRNA splicing, mRNA processing, polypeptide 16 kDa Systemic lupus erythematosus, Repeat, Methylation, 3D-structure NM_006941 SOX10 SRY (sex Transcription regulation, DNA- 3129 7097 determining region binding, Nuclear protein, Disease Y)-box 10 mutation, Hirschsprung disease, Deafness NM_006945 SPRR2B small proline-rich Keratinocyte, Repeat, Multigene 3130 7098 protein 2B family NM_006947 SRP72 signal recognition ATP-binding, Kinase, Transferase, 3131 7099 particle 72 kDa Signal recognition particle, Ribonucleoprotein NM_006987 RPH3AL rabphilin 3A-like Hypothetical protein 3132 7100 (without C2 domains) NM_006993 NPM3 nucleophosmin/nucleoplasmin, 3 Nuclear protein, Chaperone, 3133 7101 Phosphorylation NM_007000 UPK1A uroplakin 1A Hypothetical protein, 3134 7102 Transmembrane, Glycoprotein NM_007007 CPSF6 cleavage and 3135 7103 polyadenylation specific factor 6, 68 kDa NM_007008 RTN4 reticulon 4 Endoplasmic reticulum, Alternative 3136 7104 splicing, Transmembrane, Hypothetical protein NM_007014 WWP2 Nedd-4-like Ubl conjugation pathway, Ligase, 3137 7105 ubiquitin-protein Repeat ligase NM_007022 101F6 putative tumor 3138 7106 suppressor 101F6 NM_007024 PL6 placental protein 6 Transmembrane 3139 7107 NM_007032 HRIHFB2122 Tara-like protein Hypothetical protein, Cytoskeleton, 3140 7108 Actin-binding, Coiled coil, Nuclear protein NM_007033 RER1 RER1 homolog (S. cerevisiae) Transmembrane, Golgi stack 3141 7109 NM_007034 DNAJB4 DnaJ (Hsp40) Chaperone, Heat shock 3142 7110 homolog, subfamily B, member 4 NM_007043 HRB2 HIV-1 rev binding 3143 7111 protein 2 NM_007054 KIF3A kinesin family Motor protein, Microtubule, ATP- 3144 7112 member 3A binding, Coiled coil, Neurone NM_007056 SWAP2 splicing factor, mRNA processing, mRNA splicing, 3145 7113 arginine/serine-rich Nuclear protein, Alternative splicing, 16 (suppressor-of- Polymorphism white-apricot homolog, Drosophila) NM_007059 KPTN kaptin (actin binding 3146 7114 protein) NM_007062 PWP1 nuclear Repeat, WD repeat, Nuclear protein, 3147 7115 phosphoprotein Phosphorylation similar to S. cerevisiae PWP1 NM_007063 TBC1D8 TBC1 domain family, GTPase activation 3148 7116 member 8 (with GRAM domain) NM_007065 CDC37 CDC37 cell division Chaperone 3149 7117 cycle 37 homolog (S. cerevisiae) NM_007070 FAP48 glomulin, FKBP Coiled coil, Phosphorylation, 3150 7118 associated protein Alternative splicing, Disease mutation, Polymorphism NM_007074 CORO1A coronin, actin Actin-binding, Repeat, WD repeat, 3151 7119 binding protein, 1A Coiled coil, Polymorphism NM_007077 AP4S1 adaptor-related Coated pits, Endocytosis 3152 7120 protein complex 4, sigma 1 subunit NM_007098 CLTCL1 clathrin, heavy Coated pits, Alternative splicing 3153 7121 polypeptide-like 1 NM_007099 ACP1 acid phosphatase 1, Hydrolase, Acetylation, Alternative 3154 7122 soluble splicing, Polymorphism, 3D-structure NM_007108 TCEB2 transcription Transcription regulation, Ubl 3155 7123 elongation factor B conjugation pathway, Nuclear (SIII), polypeptide 2 protein, 3D-structure (18 kDa, elongin B) NM_007115 TNFAIP6 tumor necrosis Cell adhesion, Signal, Glycoprotein, 3156 7124 factor, alpha-induced Polymorphism, 3D-structure protein 6 NM_007145 ZNF146 zinc finger protein Zinc-finger, DNA-binding, Metal- 3157 7125 146 binding, Nuclear protein, Repeat NM_007152 ZNF195 zinc finger protein Zinc-finger, Metal-binding, DNA- 3158 7126 195 binding, Nuclear protein, Alternative splicing NM_007161 LST1 leukocyte specific Signal, Immune response, Cell 3159 7127 transcript 1 shape, Transmembrane, Alternative splicing, Receptor NM_007169 PEMT phosphatidylethanol Phospholipid biosynthesis, 3160 7128 amine N- Transferase, Methyltransferase, methyltransferase Transmembrane, Mitochondrion, Endoplasmic reticulum, Polymorphism NM_007172 NUP50 nucleoporin 50 kDa Hypothetical protein, Nuclear 3161 7129 protein, Transport, Protein transport, Repeat, Porin NM_007178 UNRIP unr-interacting Hypothetical protein, Repeat, WD 3162 7130 protein repeat NM_007186 CEP2 centrosomal protein 2 Cell cycle, Coiled coil, 3163 7131 Phosphorylation, Alternative splicing, Polymorphism NM_007205 TREX2 three prime repair Hypothetical protein, Proteasome, 3164 7132 exonuclease 2 Exonuclease NM_007208 MRPL3 mitochondrial Ribosomal protein, Mitochondrion 3165 7133 ribosomal protein L3 NM_007212 RNF2 ring finger protein 2 Metal-binding, Zinc, Zinc-finger 3166 7134 NM_007213 JM4 JM4 protein 3167 7135 NM_007219 RNF24 ring finger protein 24 Zinc-finger 3168 7136 NM_007222 ZHX1 zinc-fingers and Homeobox, Metal-binding, Nuclear 3169 7137 homeoboxes 1 protein, Zinc, Zinc-finger NM_007238 PXMP4 peroxisomal Peroxisome, Transmembrane, 3170 7138 membrane protein 4, Glycoprotein, Polymorphism 24 kDa NM_007240 DUSP12 dual specificity Hydrolase, Zinc, Metal-binding 3171 7139 phosphatase 12 NM_007248 TREX1 three prime repair Hypothetical protein, Exonuclease 3172 7140 exonuclease 1 NM_007255 B4GALT7 xylosylprotein beta Glycosyltransferase, Transferase, 3173 7141 1,4- Glycoprotein, Transmembrane, galactosyltransferase, Signal-anchor, Golgi stack, polypeptide 7 Multigene family, Disease mutation, (galactosyltransferase Ehlers-Danlos syndrome I) NM_007274 BACH brain acyl-CoA Hydrolase, Serine esterase, Repeat, 3174 7142 hydrolase Alternative splicing NM_007278 GABARAP GABA(A) receptor- Receptor 3175 7143 associated protein NM_007284 PTK9L protein tyrosine Hypothetical protein, Kinase 3176 7144 kinase 9-like (A6- related protein) NM_007311 BZRP benzodiazapine Mitochondrion, Receptor, 3177 7145 receptor (peripheral) Transmembrane, Polymorphism NM_007317 KIF22 kinesin family DNA-binding, Motor protein, 3178 7146 member 22 Microtubule, ATP-binding, Coiled coil, Nuclear protein NM_007318 PSEN1 presenilin 1 Transmembrane, Phosphorylation, 3179 7147 (Alzheimer disease Endoplasmic reticulum, Golgi stack, 3) Alzheimer's disease, Disease mutation, Polymorphism, Alternative splicing NM_007320 RANBP3 RAN binding protein 3 Hypothetical protein 3180 7148 NM_007334 KLRD1 killer cell lectin-like Antigen, Receptor, Glycoprotein, 3181 7149 receptor subfamily Transmembrane, Signal-anchor, D, member 1 Lectin, Alternative splicing, 3D- structure NM_007346 OGFR opioid growth factor Receptor, Growth regulation, 3182 7150 receptor Repeat, Alternative splicing NM_007360 D12S2489E killer cell lectin-like Receptor, Transmembrane, 3183 7151 receptor subfamily Multigene family, Signal-anchor, K, member 1 Lectin, Glycoprotein, Polymorphism, 3D-structure NM_007375 TARDBP TAR DNA binding DNA-binding, RNA-binding, Nuclear 3184 7152 protein protein, Transcription regulation, Repressor, mRNA processing, mRNA splicing, Repeat NM_009588 LTB lymphotoxin beta Cytokine, Transmembrane, 3185 7153 (TNF superfamily, Glycoprotein, Signal-anchor, member 3) Alternative splicing, Polymorphism NM_012062 DNM1L dynamin 1-like Hypothetical protein 3186 7154 NM_012064 MIP major intrinsic Gap junction, Transport, 3187 7155 protein of lens fiber Transmembrane, Phosphorylation, Eye lens protein NM_012079 DGAT1 diacylglycerol O- Transferase, Acyltransferase, 3188 7156 acyltransferase Transmembrane, Endoplasmic homolog 1 (mouse) reticulum, Hypothetical protein NM_012084 GLUD2 glutamate Hypothetical protein 3189 7157 dehydrogenase 2 NM_012086 GTF3C3 general transcription Hypothetical protein 3190 7158 factor IIIC, polypeptide 3, 102 kDa NM_012089 ABCB10 ATP-binding ATP-binding, Transmembrane, 3191 7159 cassette, sub-family Transport, Mitochondrion, Inner B (MDR/TAP), membrane, Transit peptide, member 10 Polymorphism NM_012094 PRDX5 peroxiredoxin 5 Antioxidant, Peroxisome, 3192 7160 Mitochondrion, Transit peptide, Alternative initiation, Polymorphism, 3D-structure NM_012100 DNPEP aspartyl Hydrolase, Aminopeptidase, 3193 7161 aminopeptidase Metalloprotease, Zinc, Hypothetical protein NM_012108 BRDG1 BCR downstream 3194 7162 signaling 1 NM_012114 CASP14 caspase 14, Hydrolase, Thiol protease, 3195 7163 apoptosis-related Apoptosis, Zymogen cysteine protease NM_012124 CHORDC1 cysteine and 3196 7164 histidine-rich domain (CHORD)- containing, zinc binding protein 1 NM_012130 CLDN14 claudin 14 Tight junction, Transmembrane, 3197 7165 Polymorphism, Disease mutation, Deafness NM_012142 CCNDBP1 cyclin D-type Cyclin, Hypothetical protein 3198 7166 binding-protein 1 NM_012143 TFIP11 tuftelin interacting Biomineralization, Nuclear protein, 3199 7167 protein 11 Alternative splicing NM_012151 F8A coagulation factor Hypothetical protein 3200 7168 VIII-associated (intronic transcript) NM_012168 FBXO2 F-box only protein 2 Ubl conjugation pathway 3201 7169 NM_012185 FOXE2 forkhead box E2 DNA-binding, Nuclear protein, 3202 7170 Transcription regulation NM_012198 GCA grancalcin, EF-hand Calcium-binding, Repeat, 3D- 3203 7171 calcium binding structure protein NM_012203 GRHPR glyoxylate Hypothetical protein, 3204 7172 reductase/hydroxypyruvate Oxidoreductase, Pyruvate reductase NM_012214 MGAT4A mannosyl (alpha- Glycosyltransferase, Transferase 3205 7173 1,3-)-glycoprotein beta-1,4-N- acetylglucosaminyltransferase, isoenzyme A NM_012218 ILF3 interleukin enhancer Hypothetical protein, Transcription 3206 7174 binding factor 3, regulation, DNA-binding, RNA- 90 kDa binding, Nuclear protein, Repeat, Phosphorylation, Methylation, Alternative splicing NM_012228 PILB pilin-like transcription Hypothetical protein 3207 7175 factor NM_012229 NT5C2 5′-nucleotidase, Hydrolase, Allosteric enzyme 3208 7176 cytosolic II NM_012236 SCMH1 sex comb on midleg 3209 7177 homolog 1 (Drosophila) NM_012244 SLC7A8 solute carrier family Hypothetical protein, Transport, 3210 7178 7 (cationic amino Amino-acid transport, acid transporter, y+ Transmembrane system), member 8 NM_012250 RRAS2 related RAS viral (r- GTP-binding, Prenylation, 3211 7179 ras) oncogene Lipoprotein, Proto-oncogene, homolog 2 Disease mutation NM_012255 XRN2 5′-3′ mRNA processing, Hydrolase, 3212 7180 exoribonuclease 2 Nuclease, Exonuclease, Nuclear protein, RNA-binding, Zinc-finger NM_012258 HEY1 hairy/enhancer-of- Hypothetical protein, Transcription 3213 7181 split related with regulation, DNA-binding, Nuclear YRPW motif 1 protein NM_012262 HS2ST1 heparan sulfate 2-O- Hypothetical protein, Transferase 3214 7182 sulfotransferase 1 NM_012282 KCNE1L potassium voltage- Transmembrane, Glycoprotein, 3215 7183 gated channel, lsk- Alport syndrome, Deafness, related family, Elliptocytosis member 1-like NM_012286 MORF4L2 mortality factor 4 like 2 Growth regulation, Nuclear protein 3216 7184 NM_012290 TLK1 tousled-like kinase 1 ATP-binding, Kinase, 3217 7185 Serine/threonine-protein kinase, Transferase, Chromatin regulator, Cell cycle, DNA damage, Nuclear protein, Coiled coil, Phosphorylation, Alternative splicing NM_012295 CABIN1 calcineurin binding Hypothetical protein, 3218 7186 protein 1 Phosphorylation, Repeat, TPR repeat NM_012329 MMD monocyte to Transmembrane 3219 7187 macrophage differentiation- associated NM_012331 MSRA methionine sulfoxide Oxidoreductase 3220 7188 reductase A NM_012341 CRFG GTP binding protein 4 GTP-binding, Nuclear protein 3221 7189 NM_012342 NMA putative Transmembrane, Signal, 3222 7190 transmembrane Glycoprotein protein NM_012343 NNT nicotinamide Oxidoreductase, NAD, NADP, 3223 7191 nucleotide Transmembrane, Mitochondrion, transhydrogenase Transit peptide, 3D-structure, Hypothetical protein NM_012347 FBXO9 F-box only protein 9 Hypothetical protein, Ubl conjugation 3224 7192 pathway, TPR repeat NM_012383 OSTF1 osteoclast Hypothetical protein, ANK repeat, 3225 7193 stimulating factor 1 Repeat, SH3 domain NM_012384 GMEB2 glucocorticoid Trans-acting factor, Nuclear protein, 3226 7194 modulatory element DNA-binding, Coiled coil binding protein 2 NM_012387 PADI4 peptidyl arginine Hydrolase, Calcium-binding, 3227 7195 deiminase, type IV Multigene family NM_012390 PROL5 proline rich 5 Saliva 3228 7196 (salivary) NM_012392 PEF PEF protein with a Calcium-binding 3229 7197 long N-terminal hydrophobic domain (peflin) NM_012400 PLA2G2D phospholipase A2, Hydrolase, Lipid degradation, Signal, 3230 7198 group IID Calcium, Polymorphism NM_012403 ANP32C acidic (leucine-rich) 3231 7199 nuclear phosphoprotein 32 family, member C NM_012413 QPCT glutaminyl-peptide Transferase, Acyltransferase, Signal, 3232 7200 cyclotransferase Polymorphism (glutaminyl cyclase) NM_012434 SLC17A5 solute carrier family Transmembrane, Hypothetical 3233 7201 17 (anion/sugar protein, Sugar transport transporter), member 5 NM_012445 SPON2 spondin 2, Hypothetical protein, Matrix protein 3234 7202 extracellular matrix protein NM_012446 SSBP2 single-stranded DNA DNA-binding, Nuclear protein 3235 7203 binding protein 2 NM_012455 TIC SEC7 homolog 3236 7204 NM_012460 TIMM9 translocase of inner Transport, Protein transport, 3237 7205 mitochondrial Translocation, Mitochondrion, Inner membrane 9 membrane, Hypothetical protein homolog (yeast) NM_012463 ATP6V0A2 ATPase, H+ Hydrogen ion transport, 3238 7206 transporting, Transmembrane, Glycoprotein, lysosomal V0 Hypothetical protein subunit a isoform 2 NM_012483 GNLY granulysin Antibiotic, Fungicide, Signal, T-cell, 3239 7207 Alternative splicing, 3D-structure NM_012484 HMMR hyaluronan- Hyaluronic acid, Alternative splicing, 3240 7208 mediated motility Repeat, Glycoprotein, Antigen receptor (RHAMM) NM_012485 HMMR hyaluronan- Hyaluronic acid, Alternative splicing, 3241 7209 mediated motility Repeat, Glycoprotein, Antigen receptor (RHAMM) NM_013229 APAF1 apoptotic protease Apoptosis, ATP-binding, Repeat, 3242 7210 activating factor WD repeat, Alternative splicing, 3D- structure NM_013235 RNASE3L nuclear RNase III Ribosome biogenesis, Hydrolase, 3243 7211 Drosha Nuclease, Endonuclease, Repeat, RNA-binding, Nuclear protein, Alternative splicing NM_013236 E46L like mouse brain Hypothetical protein 3244 7212 protein E46 NM_013242 GTL3 likely ortholog of 3245 7213 mouse gene trap locus 3 NM_013248 NXT1 NTF2-like export Transport, Protein transport, Nuclear 3246 7214 factor 1 protein, 3D-structure NM_013252 CLECSF5 C-type (calcium Transmembrane, Lectin 3247 7215 dependent, carbohydrate- recognition domain) lectin, superfamily member 5 NM_013258 ASC apoptosis- Apoptosis, Anti-oncogene, 3248 7216 associated speck- Alternative splicing like protein containing a CARD NM_013259 NP25 neuronal protein 3249 7217 NM_013272 SLC21A11 solute carrier organic Transmembrane, Transport, Ion 3250 7218 anion transporter transport, Glycoprotein family, member 3A1 NM_013285 HUMAUANTIG nucleolar GTPase GTP-binding, Nuclear protein 3251 7219 NM_013286 KIAA0800 chromosome 3p21.1 Hypothetical protein 3252 7220 gene sequence NM_013289 KIR3DL1 killer cell Receptor, Immunoglobulin domain, 3253 7221 immunoglobulin-like Glycoprotein, Signal, receptor, three Transmembrane, Repeat, Multigene domains, long family, Polymorphism, 3D-structure, cytoplasmic tail, 1 Alternative splicing NM_013296 MCLC LGN protein Hypothetical protein, Repeat, TPR 3254 7222 repeat, Phosphorylation NM_013300 HSU79274 protein predicted by Hypothetical protein 3255 7223 clone 23733 NM_013301 HSU79303 protein predicted by Hypothetical protein 3256 7224 clone 23882 NM_013312 HOOK2 hook homolog 2 Hypothetical protein 3257 7225 (Drosophila) NM_013319 TERE1 transitional epithelia 3258 7226 response protein NM_013323 SNX11 sorting nexin 11 Transport, Protein transport 3259 7227 NM_013328 P5CR2 pyrroline 5- Hypothetical protein 3260 7228 carboxylate reductase isoform NM_013330 NME7 non-metastatic cells Transferase, Kinase, ATP-binding, 3261 7229 7, protein expressed Sodium/potassium transport, in (nucleoside- Transmembrane, Glycoprotein, diphosphate kinase) Multigene family, Signal-anchor, Alternative splicing NM_013341 PTD004 hypothetical protein GTP-binding, Alternative splicing 3262 7230 PTD004 NM_013351 TBX21 T-box 21 Transcription regulation, DNA- 3263 7231 binding, Nuclear protein, Activator NM_013354 CNOT7 CCR4-NOT Transcription regulation, Repressor, 3264 7232 transcription Nuclear protein, Hypothetical protein complex, subunit 7 NM_013363 PCOLCE2 procollagen C- Collagen 3265 7233 endopeptidase enhancer 2 NM_013363 PNMA3 paraneoplastic Hypothetical protein 3266 7234 antigen MA3 NM_013368 RBT1 RPA-binding trans- Hypothetical protein 3267 7235 activator NM_013382 POMT2 protein-O- Transferase, Glycosyltransferase, 3268 7236 mannosyltransferase 2 Endoplasmic reticulum, Transmembrane, Glycoprotein, Repeat, Alternative splicing NM_013383 TCFL4 transcription factor- Transcription regulation, Repressor, 3269 7237 like 4 Nuclear protein, DNA-binding, Alternative splicing, Receptor NM_013392 NRBP nuclear receptor Hypothetical protein, ATP-binding, 3270 7238 binding protein Transferase, Nuclear protein, Receptor NM_013395 AD013 Homo sapiens Hypothetical protein, 3271 7239 proteinx0008 Transmembrane (AD013) mRNA, complete cds. NM_013403 STRN4 striatin, calmodulin Calmodulin-binding, Repeat, WD 3272 7240 binding protein 4 repeat, Coiled coil NM_013412 RABL2A RAB, member of Hypothetical protein, GTP-binding, 3273 7241 RAS oncogene Alternative splicing family-like 2A NM_013416 NCF4 neutrophil cytosolic SH3 domain, Alternative splicing, 3274 7242 factor 4, 40 kDa 3D-structure NM_013421 GGT1 gamma- Glutathione biosynthesis, 3275 7243 glutamyltransferase 1 Transferase, Acyltransferase, Signal-anchor, Transmembrane, Zymogen, Glycoprotein, Sialic acid, Alternative splicing, Alternative promoter usage NM_013430 GGT1 gamma- Glutathione biosynthesis, 3276 7244 glutamyltransferase 1 Transferase, Acyltransferase, Signal-anchor, Transmembrane, Zymogen, Glycoprotein, Sialic acid, Alternative splicing, Alternative promoter usage NM_013439 PILR(ALPHA) paired Receptor 3277 7245 immunoglobin-like type 2 receptor alpha NM_013440 PILR(BETA) paired Meiosis, Cell cycle, Chromosome 3278 7246 immunoglobin-like partition, Nuclear protein, Alternative type 2 receptor beta splicing, Hypothetical protein, Receptor NM_013444 UBQLN2 ubiquilin 2 Hypothetical protein 3279 7247 NM_013448 BAZ1A bromodomain Transcription regulation, 3280 7248 adjacent to zinc Bromodomain, Zinc-finger, Coiled finger domain, 1A coil, Nuclear protein, Alternative splicing NM_013940 OR10H1 olfactory receptor, 3281 7249 family 10, subfamily H, member 1 NM_013943 CLIC4 chloride intracellular Hypothetical protein, Ionic channel, 3282 7250 channel 4 Ion transport, Chloride channel, Voltage-gated channel NM_013951 PAX8 paired box gene 8 DNA-binding, Developmental 3283 7251 protein, Nuclear protein, Paired box, Transcription, Transcription regulation, Differentiation, Alternative splicing, Disease mutation, Polymorphism NM_013956 NRG1 neuregulin 1 EGF-like domain, Growth factor, 3284 7252 Transmembrane, Multigene family, Alternative splicing, Immunoglobulin domain, Glycoprotein, Polymorphism, 3D-structure, Chromosomal translocation NM_013974 DDAH2 dimethylarginine Hydrolase 3285 7253 dimethylaminohydrolase 2 NM_013975 LIG3 ligase III, DNA, ATP- DNA repair, DNA replication, DNA 3286 7254 dependent recombination, Cell division, Ligase, ATP-binding, Zinc-finger, Nuclear protein, Alternative splicing, 3D- structure, Hypothetical protein NM_013979 BNIP1 BCL2/adenovirus Apoptosis, Alternative splicing, 3287 7255 E1B 19 kDa Transmembrane interacting protein 1 NM_013992 PAX8 paired box gene 8 DNA-binding, Developmental 3288 7256 protein, Nuclear protein, Paired box, Transcription, Transcription regulation, Differentiation, Alternative splicing, Disease mutation, Polymorphism NM_013995 LAMP2 lysosomal- Transmembrane, Glycoprotein, 3289 7257 associated Lysosome, Signal, Alternative membrane protein 2 splicing, Polymorphism NM_014000 VCL vinculin Cell adhesion, Actin-binding, 3290 7258 Cytoskeleton, Structural protein, Phosphorylation, Repeat, Alternative splicing, Lipoprotein NM_014011 SOCS5 suppressor of SH2 domain, Growth regulation, 3291 7259 cytokine signaling 5 Signal transduction inhibitor NM_014018 MRPS28 mitochondrial Ribosomal protein, Mitochondrion 3292 7260 ribosomal protein S28 NM_014029 RAC2 ras-related C3 GTP-binding, Prenylation, 3293 7261 botulinum toxin Lipoprotein, 3D-structure substrate 2 (rho family, small GTP binding protein Rac2) NM_014030 GIT1 G protein-coupled Hypothetical protein, GTPase 3294 7262 receptor kinase- activation, Repeat, ANK repeat, interactor 1 Zinc-finger NM_014038 BZW2 basic leucine zipper Hypothetical protein 3295 7263 and W2 domains 2 NM_014042 DKFZP564M082 DKFZP564M082 Hypothetical protein 3296 7264 protein NM_014050 MRPL42 mitochondrial Ribosomal protein, Mitochondrion 3297 7265 ribosomal protein L42 NM_014051 PTD011 transmembrane Transmembrane 3298 7266 protein 14A NM_014052 GW128 GW128 protein 3299 7267 NM_014055 CDV-1 carnitine deficiency- Hypothetical protein 3300 7268 associated gene expressed in ventricle 1 NM_014056 HIG1 likely ortholog of Hypothetical protein 3301 7269 mouse hypoxia induced gene 1 NM_014060 MCT-1 malignant T cell 3302 7270 amplified sequence 1 NM_014061 MAGEH1 APR-1 protein Antigen 3303 7271 NM_014062 ART-4 likely ortholog of Hypothetical protein 3304 7272 mouse nin one binding protein NM_014063 HIP-55 src homology 3 Hypothetical protein, SH3 domain 3305 7273 domain-containing protein HIP-55 NM_014078 MRPL13 mitochondrial Ribosomal protein, Mitochondrion 3306 7274 ribosomal protein L13 NM_014080 DUOX2 dual oxidase 2 Peroxidase 3307 7275 NM_014147 CAPRI HSPC047 protein GTPase activation, Repeat 3308 7276 NM_014165 C6orf66 chromosome 6 open 3309 7277 reading frame 66 NM_014170 HSPC135 HSPC135 protein Hypothetical protein 3310 7278 NM_014175 MRPL15 mitochondrial Hypothetical protein 3311 7279 ribosomal protein L15 NM_014177 HSPC154 HSPC154 protein 3312 7280 NM_014180 MRPL22 mitochondrial Hypothetical protein, Ribosomal 3313 7281 ribosomal protein protein L22 NM_014182 ORMDL2 ORM1-like 2 (S. cerevisiae) Hypothetical protein, Nuclear 3314 7282 protein, DNA-binding, Transcription, Transcription regulation, Translation regulation, Receptor NM_014184 HSPC163 HSPC163 protein Hypothetical protein, 3315 7283 Transmembrane NM_014204 BOK Homo sapiens Bcl-2 3316 7284 related ovarian killer (BOK) mRNA, complete cds. NM_014207 CD5 CD5 antigen (p56-62) Signal, Transmembrane, 3317 7285 Glycoprotein, T-cell, Repeat NM_014214 IMPA2 inositol(myo)-1(or 4)- Hydrolase 3318 7286 monophosphatase 2 NM_014216 ITPK1 inositol 1,3,4- Kinase, Hypothetical protein 3319 7287 triphosphate 5/6 kinase NM_014221 MTCP1 mature T-cell Proto-oncogene, Mitochondrion, 3320 7288 proliferation 1 Alternative splicing, Chromosomal translocation, 3D-structure NM_014223 NFYC nuclear transcription Transcription regulation, DNA- 3321 7289 factor Y, gamma binding, Activator, Nuclear protein, Alternative splicing, 3D-structure NM_014225 PPP2R1A protein phosphatase Hypothetical protein, Multigene 3322 7290 2 (formerly 2A), family, Acetylation, Repeat, regulatory subunit A Polymorphism, 3D-structure (PR 65), alpha isoform NM_014231 VAMP1 vesicle-associated Mitochondrion, Synapse, 3323 7291 membrane protein 1 Synaptosome, Transmembrane, (synaptobrevin 1) Coiled coil, Alternative splicing, Multigene family NM_014232 VAMP2 vesicle-associated Hypothetical protein, Synapse, 3324 7292 membrane protein 2 Synaptosome, Transmembrane, (synaptobrevin 2) Coiled coil, Acetylation, Multigene family, 3D-structure NM_014239 EIF2B2 eukaryotic Initiation factor, Protein biosynthesis, 3325 7293 translation initiation Disease mutation factor 2B, subunit 2 beta, 39 kDa NM_014241 PTPLA protein tyrosine ATP-binding, Chaperone 3326 7294 phosphatase-like (proline instead of catalytic arginine), member a NM_014242 ZNF237 zinc finger protein 3327 7295 237 NM_014245 RNF7 ring finger protein 7 Ubl conjugation pathway, Zinc, Zinc- 3328 7296 finger, Metal-binding, Phosphorylation, Alternative splicing NM_014252 SLC25A15 solute carrier family Mitochondrion, Inner membrane, 3329 7297 25 (mitochondrial Repeat, Transmembrane, Transport, carrier; ornithine Disease mutation, Polymorphism transporter) member 15 NM_014253 ODZ1 odz, odd Oz/ten-m EGF-like domain 3330 7298 homolog 1 (Drosophila) NM_014254 TMEM5 transmembrane Transmembrane 3331 7299 protein 5 NM_014268 MAPRE2 microtubule- T-cell 3332 7300 associated protein, RP/EB family, member 2 NM_014280 DNAJC8 DnaJ (Hsp40) Chaperone 3333 7301 homolog, subfamily C, member 8 NM_014292 CBX6 chromobox homolog 6 Chromatin regulator, Nuclear 3334 7302 protein, Transcription regulation, Repressor NM_014297 YF13H12 ethylmalonic 3335 7303 encephalopathy 1 NM_014306 HSPC117 hypothetical protein Hypothetical protein 3336 7304 HSPC117 NM_014313 SMP1 small membrane Transmembrane, Polymorphism 3337 7305 protein 1 NM_014326 DAPK2 death-associated Transferase, Serine/threonine- 3338 7306 protein kinase 2 protein kinase, Calmodulin-binding, Phosphorylation, ATP-binding, Apoptosis NM_014330 PPP1R15A protein phosphatase Hypothetical protein 3339 7307 1, regulatory (inhibitor) subunit 15A NM_014335 CRI1 CREBBP/EP300 Hypothetical protein 3340 7308 inhibitory protein 1 NM_014339 IL17R interleukin 17 Receptor, Transmembrane, Signal, 3341 7309 receptor Glycoprotein NM_014341 MTCH1 mitochondrial carrier 3342 7310 homolog 1 (C. elegans) NM_014343 CLDN15 claudin 15 Tight junction, Transmembrane 3343 7311 NM_014350 GG2-1 TNF-induced protein 3344 7312 NM_014357 XP5 small proline rich-like 3345 7313 (epidermal differentiation complex) 1B NM_014359 OPTC opticin Glycoprotein, Extracellular matrix, 3346 7314 Signal, Repeat, Leucine-rich repeat, Sulfation NM_014362 HIBCH 3-hydroxyisobutyryl- Hydrolase 3347 7315 Coenzyme A hydrolase NM_014366 E2IG3 nucleostemin Hypothetical protein 3348 7316 NM_014373 GPCR1 G protein-coupled Receptor 3349 7317 receptor 160 NM_014381 MLH3 mutL homolog 3 (E. coli) DNA repair, Nuclear protein, 3350 7318 Polymorphism, Alternative splicing, Hereditary nonpolyposis colorectal cancer, Disease mutation, Hypothetical protein NM_014399 NET-6 transmembrane 4 Glycoprotein, Transmembrane 3351 7319 superfamily member 13 NM_014403 SIAT7D sialyltransferase 7D Transferase, Glycosyltransferase, 3352 7320 ((alpha-N- Glycoprotein, Transmembrane, acetylneuraminyl- Signal-anchor, Golgi stack 2,3-beta-galactosyl- 1,3)-N-acetyl galactosaminide alpha-2,6- sialyltransferase) NM_014413 HRI heme-regulated Transferase, Kinase, 3353 7321 initiation factor 2- Serine/threonine-protein kinase, alpha kinase Protein synthesis inhibitor, ATP- binding, Repeat, Phosphorylation, Alternative splicing, Polymorphism, Protein biosynthesis NM_014425 INVS inversin ANK repeat, Repeat 3354 7322 NM_014426 SNX5 sorting nexin 5 Transport, Protein transport, 3355 7323 Hypothetical protein NM_014430 CIDEB cell death-inducing Apoptosis, 3D-structure, RNA- 3356 7324 DFFA-like effector b binding, Repeat, G-protein coupled receptor, Transmembrane, Glycoprotein NM_014434 NR1 NADPH-dependent 3357 7325 FMN and FAD containing oxidoreductase NM_014437 SLC39A1 solute carrier family Transport, Zinc transport, 3358 7326 39 (zinc transporter), Transmembrane member 1 NM_014446 MIBP integrin beta 1 3359 7327 binding protein 3 NM_014450 SIT SHP2-interacting Signal 3360 7328 transmembrane adaptor protein NM_014453 BC-2 putative breast 3361 7329 adenocarcinoma marker (32 kD) NM_014465 SULT1B1 sulfotransferase Hypothetical protein, Transferase 3362 7330 family, cytosolic, 1B, member 1 NM_014473 HSA9761 putative rRNA processing, Transferase, 3363 7331 dimethyladenosine Methyltransferase transferase NM_014481 APEX2 APEX nuclease Endonuclease 3364 7332 (apurinic/apyrimidinic endonuclease) 2 NM_014499 P2RY10 purinergic receptor Receptor, Transmembrane 3365 7333 P2Y, G-protein coupled, 10 NM_014503 DRIM down-regulated in 3366 7334 metastasis NM_014517 UBP1 upstream binding Hypothetical protein 3367 7335 protein 1 (LBP-1a) NM_014520 MYBBP1A MYB binding protein Hypothetical protein 3368 7336 (P160) 1a NM_014575 SCHIP1 schwannomin Hypothetical protein 3369 7337 interacting protein 1 NM_014593 CGBP CpG binding protein Hypothetical protein, Transcription 3370 7338 regulation, Activator, DNA-binding, Zinc-finger, Metal-binding, Coiled coil, Nuclear protein NM_014624 S100A6 S100 calcium Mitogen, Cell cycle, Calcium-binding, 3371 7339 binding protein A6 Polymorphism, 3D-structure (calcyclin) NM_014630 KIAA0211 KIAA0211 gene Hypothetical protein, Transcription 3372 7340 product regulation, DNA-binding, Zinc-finger, Metal-binding, Nuclear protein, Repeat NM_014638 KIAA0450 KIAA0450 gene Hypothetical protein 3373 7341 product NM_014639 KIAA0372 KIAA0372 Hypothetical protein 3374 7342 NM_014659 KIAA0377 KIAA0377 gene Hypothetical protein 3375 7343 product NM_014671 KIAA0010 ubiquitin-protein Hypothetical protein, Ligase 3376 7344 isopeptide ligase (E3) NM_014675 KIAA0445 ciliary rootlet coiled- Hypothetical protein 3377 7345 coil, rootletin NM_014678 KIAA0685 KIAA0685 Hypothetical protein 3378 7346 NM_014684 KIAA0373 KIAA0373 gene Hypothetical protein, Coiled coil 3379 7347 product NM_014685 HERPUD1 homocysteine- Hypothetical protein, Unfolded 3380 7348 inducible, protein response, Endoplasmic endoplasmic reticulum, Transmembrane, reticulum stress- Alternative splicing inducible, ubiquitin- like domain member 1 NM_014688 RNTRE USP6 N-terminal like Hypothetical protein 3381 7349 NM_014698 KIAA0792 KIAA0792 gene Hypothetical protein 3382 7350 product NM_014699 KIAA0296 KIAA0296 gene Hypothetical protein, Transcription 3383 7351 product regulation, DNA-binding, Zinc-finger, Metal-binding, Nuclear protein, Repeat NM_014707 HDAC9 histone deacetylase 9 Hydrolase, Nuclear protein, 3384 7352 Chromatin regulator, Transcription regulation, Repressor, Alternative splicing, Hypothetical protein NM_014710 KIAA0443 G protein-coupled Hypothetical protein 3385 7353 receptor-associated sorting protein NM_014716 CENTB1 centaurin, beta 1 GTPase activation, Repeat, ANK 3386 7354 repeat, Zinc-finger NM_014718 CLSTN3 calsyntenin 3 Cell adhesion, Glycoprotein, 3387 7355 Transmembrane, Calcium-binding, Repeat, Signal NM_014724 ZNF305 zinc finger protein Transcription regulation, DNA- 3388 7356 305 binding, Zinc-finger, Metal-binding, Nuclear protein, Repeat NM_014727 WBP7 myeloid/lymphoid or DNA-binding, Bromodomain, 3389 7357 mixed-lineage Nuclear protein, Zinc-finger, Metal- leukemia 4 binding, Transcription regulation, Alternative splicing, Repeat NM_014729 TOX thymus high mobility Hypothetical protein 3390 7358 group box protein TOX NM_014732 KIAA0513 KIAA0513 gene Hypothetical protein 3391 7359 product NM_014735 KIAA0215 PHD finger protein Zinc-finger 3392 7360 16 NM_014737 RASSF2 Ras association Hypothetical protein 3393 7361 (RaIGDS/AF-6) domain family 2 NM_014739 BTF Bcl-2-associated Hypothetical protein 3394 7362 transcription factor NM_014740 KIAA0111 DEAD (Asp-Glu-Ala- ATP-binding, RNA-binding, DNA- 3395 7363 Asp) box polypeptide binding, Helicase, Nuclear protein, 48 rRNA processing NM_014750 DLG7 discs, large homolog Hypothetical protein 3396 7364 7 (Drosophila) NM_014751 MTSS1 metastasis Cytoskeleton, Actin-binding, Coiled 3397 7365 suppressor 1 coil, Anti-oncogene, Alternative splicing NM_014753 KIAA0187 BMS1-like, ribosome Ribosome biogenesis, Nuclear 3398 7366 assembly protein protein, ATP-binding (yeast) NM_014763 MRPL19 mitochondrial Ribosomal protein, Mitochondrion, 3399 7367 ribosomal protein Transit peptide L19 NM_014764 DAZAP2 DAZ associated Hypothetical protein 3400 7368 protein 2 NM_014765 TOMM20- translocase of outer Transport, Protein transport, Outer 3401 7369 PENDING mitochondrial membrane, Mitochondrion, membrane 20 Transmembrane homolog (yeast) NM_014767 SPOCK2 sparc/osteonectin, Extracellular matrix, Proteoglycan, 3402 7370 cwcv and kazal-like Heparan sulfate, Glycoprotein, domains Calcium-binding, Signal proteoglycan (testican) 2 NM_014776 GIT2 G protein-coupled GTPase activation, Repeat, ANK 3403 7371 receptor kinase- repeat, Zinc-finger, Alternative interactor 2 splicing, Hypothetical protein NM_014792 KIAA0125 KIAA0125 Hypothetical protein 3404 7372 NM_014807 KIAA0285 KIAA0285 gene Hypothetical protein 3405 7373 product NM_014808 FARP2 FERM, RhoGEF and Hypothetical protein 3406 7374 pleckstrin domain protein 2 NM_014815 TRAP100 thyroid hormone Transcription regulation, Zinc-finger, 3407 7375 receptor-associated Repeat, ATP-binding, Nuclear protein (100 kDa) protein NM_014820 TOMM70A translocase of outer Mitochondrion, Outer membrane, 3408 7376 mitochondrial Transmembrane, Repeat, TPR membrane 70 repeat homolog A (yeast) NM_014830 KIAA0352 KIAA0352 gene Hypothetical protein, Transcription 3409 7377 product regulation, DNA-binding, Zinc-finger, Metal-binding, Nuclear protein, Repeat NM_014835 OSBPL2 oxysterol binding Lipid transport, Transport, 3410 7378 protein-like 2 Alternative splicing NM_014838 ZBED4 zinc finger, BED Repeat, Zinc-finger 3411 7379 domain containing 4 NM_014844 KIAA0329 KIAA0329 Hypothetical protein 3412 7380 NM_014846 KIAA0196 KIAA0196 gene Hypothetical protein 3413 7381 product NM_014861 KIAA0703 KIAA0703 gene Hydrolase, Calcium transport, 3414 7382 product Transmembrane, Phosphorylation, ATP-binding, Metal-binding, Magnesium, Calcium-binding, Multigene family NM_014863 GALNAC4S- B cell RAG Hypothetical protein, Transferase 3415 7383 6ST associated protein NM_014865 CNAP1 chromosome DNA condensation, Mitosis, Cell 3416 7384 condensation-related cycle, Nuclear protein, SMC-associated Phosphorylation protein 1 NM_014869 KIAA0763 KIAA0763 gene Hypothetical protein 3417 7385 product NM_014872 KIAA0354 zinc finger and BTB Hypothetical protein, Metal-binding, 3418 7386 domain containing 5 Zinc, Zinc-finger NM_014873 KIAA0205 KIAA0205 gene Hypothetical protein, Phospholipid 3419 7387 product biosynthesis, Transferase, Acyltransferase, Transmembrane NM_014874 MFN2 mitofusin 2 Hypothetical protein 3420 7388 NM_014878 KIAA0020 minor Hypothetical protein, RNA-binding, 3421 7389 histocompatibility Repeat, Nuclear protein antigen HA-8 NM_014882 KIAA0053 KIAA0053 gene Hypothetical protein 3422 7390 product NM_014886 YR-29 TGF beta-inducible Nuclear protein 3423 7391 nuclear protein 1 NM_014888 FAM3C family with sequence Signal 3424 7392 similarity 3, member C NM_014889 PITRM1 pitrilysin Metalloprotease, Protease, 3425 7393 metalloproteinase 1 Hypothetical protein NM_014897 KIAA0924 KIAA0924 protein Hypothetical protein, Metal-binding, 3426 7394 Nuclear protein, Zinc, Zinc-finger NM_014899 RHOBTB3 Rho-related BTB Repeat 3427 7395 domain containing 3 NM_014902 KIAA0964 disks large- Membrane, Alternative splicing 3428 7396 associated protein 4 NM_014907 KIAA0967 KIAA0967 protein Hypothetical protein 3429 7397 NM_014913 KIAA0863 KIAA0863 protein Hypothetical protein, Metal-binding, 3430 7398 Zinc, Zinc-finger NM_014915 KIAA1074 KIAA1074 protein ANK repeat, Repeat, Hypothetical 3431 7399 protein NM_014929 KIAA0971 KIAA0971 protein Hypothetical protein 3432 7400 NM_014931 KIAA1115 KIAA1115 protein Hypothetical protein 3433 7401 NM_014937 SAC2 inositol Hypothetical protein 3434 7402 polyphosphate-5- phosphatase F NM_014940 KIAA0872 HSV-1 stimulation- Hypothetical protein 3435 7403 related gene 1 NM_014944 CLSTN1 calsyntenin 1 Cell adhesion, Glycoprotein, 3436 7404 Transmembrane, Calcium-binding, Repeat, Signal NM_014947 KIAA1041 KIAA1041 protein Hypothetical protein, Transcription 3437 7405 regulation, DNA-binding, Nuclear protein NM_014949 KIAA0907 KIAA0907 protein Hypothetical protein 3438 7406 NM_014953 DIS3 mitotic control Exosome, Hydrolase, Nuclease, 3439 7407 protein dis3 homolog Exonuclease, rRNA processing, Nuclear protein, RNA-binding, Hypothetical protein NM_014965 KIAA1042 OGT(O-Glc-NAc Glycoprotein, Coiled coil, 3440 7408 transferase)- Hypothetical protein interacting protein 106 KDa NM_014966 DDX30 DEAH (Asp-Glu-Ala- ATP-binding, Helicase, Hydrolase, 3441 7409 His) box polypeptide Hypothetical protein 30 NM_014967 KIAA1018 KIAA1018 protein Hypothetical protein 3442 7410 NM_014977 ACINUS apoptotic chromatin Apoptosis, Nuclear protein, 3443 7411 condensation Alternative splicing inducer in the nucleus NM_015057 KIAA0916 protein associated Hypothetical protein 3444 7412 with Myc NM_015156 RCOR REST corepressor DNA-binding, Nuclear protein, 3445 7413 Hypothetical protein NM_015239 AGTPBP1 ATP/GTP binding Hypothetical protein 3446 7414 protein 1 NM_015310 EFA6R ADP-ribosylation Hypothetical protein, Guanine- 3447 7415 factor guanine nucleotide releasing factor nucleotide factor 6 NM_015361 R3HDM R3H domain (binds Hypothetical protein 3448 7416 single-stranded nucleic acids) containing NM_015368 PANX1 pannexin 1 Gap junction, Transmembrane, 3449 7417 Polymorphism NM_015379 BRI3 brain protein I3 Transmembrane 3450 7418 NM_015383 DJ328E19.C1.1 hypothetical protein Hypothetical protein 3451 7419 DJ328E19.C1.1 NM_015392 NPDC1 neural proliferation, Hypothetical protein, Signal, 3452 7420 differentiation and Transmembrane control, 1 NM_015400 DKFZP586N0721 DKFZP586N0721 Hypothetical protein 3453 7421 protein NM_015420 DKFZP564O0463 DKFZP564O0463 Repeat, WD repeat, Mitochondrion, 3454 7422 protein Inner membrane, Transmembrane, Transport, Hypothetical protein NM_015462 DKFZP586L0724 DKFZP586L0724 Hypothetical protein 3455 7423 protein NM_015492 DKFZP434H132 DKFZP434H132 Hypothetical protein 3456 7424 protein NM_015515 KRT23 keratin 23 (histone Hypothetical protein, Intermediate 3457 7425 deacetylase filament, Coiled coil, Keratin inducible) NM_015524 C6orf4 chromosome 6 open Alternative splicing 3458 7426 reading frame 4 NM_015527 DKFZP434P1750 DKFZP434P1750 Hypothetical protein 3459 7427 protein NM_015530 GORASP2 golgi reassembly Hypothetical protein 3460 7428 stacking protein 2, 55 kDa NM_015556 KIAA0440 signal-induced Hypothetical protein 3461 7429 proliferation- associated 1 like 1 NM_015599 PGM3 phosphoglucomutase 3 Hypothetical protein, Isomerase, 3462 7430 Phosphorylation, Polymorphism NM_015610 DKFZP434J154 DKFZP434J154 Repeat, WD repeat, Hypothetical 3463 7431 protein protein NM_015629 PRPF31 TCF3 (E2A) fusion Hypothetical protein 3464 7432 partner (in childhood Leukemia) NM_015640 PAI-RBP1 PAI-1 mRNA-binding Hypothetical protein 3465 7433 protein NM_015644 ARPC4 actin related protein Cytoskeleton, Hypothetical protein, 3466 7434 2/3 complex, subunit Ligase 4, 20 kDa NM_015654 DKFZP564C103 DKFZP564C103 Hypothetical protein 3467 7435 protein NM_015684 ATP5S ATP synthase, H+ Hydrogen ion transport, CF(0), 3468 7436 transporting, Mitochondrion, Transit peptide, mitochondrial F0 Hypothetical protein complex, subunit s (factor B) NM_015696 CL683 glutathione Hypothetical protein, 3469 7437 peroxidase 6 Oxidoreductase, Peroxidase, Signal NM_015699 DJ159A19.3 hypothetical protein Hypothetical protein 3470 7438 DJ159A19.3 NM_015711 GLTSCR1 glioma tumor 3471 7439 suppressor candidate region gene 1 NM_015722 CALCYON calcyon protein Transmembrane, Glycoprotein 3472 7440 NM_015836 WARS2 tryptophanyl tRNA Aminoacyl-tRNA synthetase, Protein 3473 7441 synthetase 2 biosynthesis, Ligase, ATP-binding, (mitochondrial) Mitochondrion, Transit peptide NM_015838 FCN2 ficolin Lectin, Collagen, Repeat, 3474 7442 (collagen/fibrinogen Glycoprotein, Signal, Multigene domain containing family lectin) 2 (hucolin) NM_015839 FCN2 ficolin Lectin, Collagen, Repeat, 3475 7443 (collagen/fibrinogen Glycoprotein, Signal, Multigene domain containing family lectin) 2 (hucolin) NM_015853 LOC51035 ORF Hypothetical protein 3476 7444 NM_015855 WIT-1 Wilms tumor Polymorphism 3477 7445 associated protein NM_015868 KIR2DL3 killer cell Receptor, Immunoglobulin domain, 3478 7446 immunoglobulin-like Glycoprotein, Signal, receptor, two Transmembrane, Repeat, Multigene domains, long family, Polymorphism, 3D-structure, cytoplasmic tail, 3 Alternative splicing NM_015872 ZFP67 zinc finger protein 67 Metal-binding, Zinc, Zinc-finger 3479 7447 homolog (mouse) NM_015905 TIF1 transcriptional Elongation factor, Protein 3480 7448 intermediary factor 1 biosynthesis, GTP-binding, Methylation, Multigene family, Transcription regulation, Repressor, DNA-binding, Bromodomain, Zinc- finger, Alternative splicing, Nuclear protein, Coiled coil, Repeat NM_015907 LAP3 leucine Hydrolase, Aminopeptidase, 3481 7449 aminopeptidase 3 Acetylation, Zinc, Magnesium, Manganese NM_015908 ARS2 arsenate resistance Hypothetical protein, Alternative 3482 7450 protein ARS2 splicing NM_015932 C13orf12 chromosome 13 Hypothetical protein 3483 7451 open reading frame 12 NM_015942 LOC51001 CGI-12 protein Hypothetical protein 3484 7452 NM_015945 OVCOV1 solute carrier family Hypothetical protein 3485 7453 35, member C2 NM_015956 MRPL4 mitochondrial Ribosomal protein 3486 7454 ribosomal protein L4 NM_015958 LOC51611 CGI-30 protein Transferase, Methyltransferase, 3487 7455 Alternative splicing, Hypothetical protein NM_015959 LOC51075 thioredoxin-related Hypothetical protein 3488 7456 transmembrane protein 2 NM_015963 LOC51078 THAP domain Zinc-finger, DNA-binding 3489 7457 containing 4 NM_015967 PTPN22 protein tyrosine Hydrolase, Alternative splicing, 3490 7458 phosphatase, non- Hypothetical protein receptor type 22 (lymphoid) NM_015971 MRPS7 mitochondrial Ribosomal protein 3491 7459 ribosomal protein S7 NM_015984 UCHL5 ubiquitin carboxyl- Hypothetical protein, Ubl conjugation 3492 7460 terminal hydrolase pathway, Hydrolase, Thiol protease, L5 Proteasome, Alternative splicing, Polymorphism NM_015999 LOC51094 adiponectin receptor 1 Fatty acid metabolism, Lipid 3493 7461 metabolism, Receptor, Transmembrane NM_016006 CGI-58 abhydrolase domain Hypothetical protein 3494 7462 containing 5 NM_016017 UCHL5 ubiquitin carboxyl- Hypothetical protein, Hydrolase, Ubl 3495 7463 terminal hydrolase conjugation pathway, Thiol protease, L5 Proteasome, Alternative splicing, Polymorphism NM_016022 LOC51107 likely ortholog of C. elegans Transmembrane, Golgi stack, 3496 7464 anterior Endoplasmic reticulum, Alternative pharynx defective 1A splicing NM_016026 RDH11 retinol Oxidoreductase, NADP, Signal- 3497 7465 dehydrogenase 11 anchor, Transmembrane, (all-trans and 9-cis) Endoplasmic reticulum, Alternative splicing NM_016039 LOC51637 chromosome 14 Hypothetical protein 3498 7466 open reading frame 166 NM_016045 C20orf45 chromosome 20 3499 7467 open reading frame 45 NM_016052 LOC51018 CGI-115 protein 3500 7468 NM_016055 MRPL48 mitochondrial Ribosomal protein, Mitochondrion 3501 7469 ribosomal protein L48 NM_016056 LOC51643 CGI-119 protein Transmembrane, Polymorphism 3502 7470 NM_016058 LOC51002 CGI-121 protein 3503 7471 NM_016064 PILB methionine sulfoxide Hypothetical protein 3504 7472 reductase B NM_016072 LOC51026 CGI-141 protein Hypothetical protein, 3505 7473 Transmembrane NM_016075 C13orf9 chromosome 13 Hypothetical protein 3506 7474 open reading frame 9 NM_016082 CDK5RAP1 CDK5 regulatory Alternative splicing 3507 7475 subunit associated protein 1 NM_016093 RPL26L1 ribosomal protein Ribosomal protein 3508 7476 L26-like 1 NM_016096 LOC51123 HSPC038 protein Metal-binding, Zinc, Zinc-finger 3509 7477 NM_016101 HSPC031 comparative gene Hypothetical protein 3510 7478 identification transcript 37 NM_016120 RNF12 ring finger protein 12 Hypothetical protein, Metal-binding, 3511 7479 Zinc, Zinc-finger, Transcription regulation NM_016122 LOC51134 NY-REN-58 antigen 3512 7480 NM_016126 LOC51668 HSPCO34 protein 3513 7481 NM_016127 MGC8721 hypothetical protein Hypothetical protein 3514 7482 MGC8721 NM_016129 COPS4 COP9 constitutive Hypothetical protein 3515 7483 photomorphogenic homolog subunit 4 (Arabidopsis) NM_016143 NSFL1C NSFL1 (p97) Hypothetical protein 3516 7484 cofactor (p47) NM_016167 RANBP9 retinoic acid Hypothetical protein 3517 7485 repressible protein NM_016175 SQSTM1 truncated calcium Hypothetical protein 3518 7486 binding protein NM_016183 C1orf33 chromosome 1 open Hypothetical protein, Ribosomal 3519 7487 reading frame 33 protein NM_016184 CLECSF6 C-type (calcium Receptor, Lectin 3520 7488 dependent, carbohydrate- recognition domain) lectin, superfamily member 6 NM_016187 BIN2 bridging integrator 2 Hypothetical protein 3521 7489 NM_016194 GNB5 guanine nucleotide Repeat, WD repeat, Transducer, 3522 7490 binding protein (G Alternative splicing, Multigene family, protein), beta 5 Hypothetical protein NM_016199 LSM7 LSM7 homolog, U6 Nuclear protein, Ribonucleoprotein, 3523 7491 small nuclear RNA mRNA splicing, mRNA processing, associated (S. cerevisiae) RNA-binding NM_016202 LOC51157 LDL induced EC Metal-binding, Zinc, Zinc-finger 3524 7492 protein NM_016207 CPSF3 cleavage and mRNA processing, Nuclear protein, 3525 7493 polyadenylation RNA-binding specific factor 3, 73 kDa NM_016208 VPS28 vacuolar protein Transport, Protein transport 3526 7494 sorting 28 (yeast) NM_016214 COL18A1 collagen, type XVIII, Collagen, Extracellular matrix, 3527 7495 alpha 1 Connective tissue, Repeat, Hydroxylation, Cell adhesion, Glycoprotein, Signal, Alternative splicing, Polymorphism, 3D-structure NM_016221 DCTN4 dynactin 4 (p62) Hypothetical protein 3528 7496 NM_016229 LOC51700 cytochrome b5 Hypothetical protein 3529 7497 reductase b5R.2 NM_016237 ANAPC5 anaphase promoting Ubl conjugation pathway, Cell cycle, 3530 7498 complex subunit 5 Cell division, Mitosis, Repeat, TPR repeat, Alternative splicing NM_016258 HGRG8 high-glucose- 3531 7499 regulated protein 8 NM_016271 RNF138 ring finger protein Hypothetical protein, Metal-binding, 3532 7500 138 Zinc, Zinc-finger NM_016274 CKIP-1 CK2 interacting Hypothetical protein 3533 7501 protein 1; HQ0024c protein NM_016283 TAF9 TAF9 RNA ATP-binding, Transcription 3534 7502 polymerase II, TATA regulation, Nuclear protein, box binding protein Polymorphism, Hypothetical protein, (TBP)-associated Cell cycle factor, 32 kDa NM_016293 BIN2 bridging integrator 2 Hypothetical protein 3535 7503 NM_016299 HSP70-4 likely ortholog of ATP-binding 3536 7504 mouse heat shock protein, 70 kDa 4 NM_016304 C15orf15 chromosome 15 Ribosomal protein 3537 7505 open reading frame 15 NM_016306 DNAJB11 DnaJ (Hsp40) Chaperone, Endoplasmic reticulum, 3538 7506 homolog, subfamily Signal, Polymorphism B, member 11 NM_016309 LCMT1 leucine carboxyl Hypothetical protein, 3539 7507 methyltransferase 1 Methyltransferase, Transferase NM_016312 WBP11 WW domain binding Hypothetical protein 3540 7508 protein 11 NM_016316 REV1L REV1-like (yeast) Transferase, Integrin, Hypothetical 3541 7509 protein NM_016326 CKLF chemokine-like Chemotaxis, Cytokine, 3542 7510 factor Transmembrane, Alternative splicing NM_016327 UPB1 ureidopropionase, Hydrolase, Allosteric enzyme, Zinc 3543 7511 beta NM_016331 LOC51193 zinc finger protein Metal-binding, Zinc, Zinc-finger 3544 7512 ANC_2H01 NM_016332 SEPX1 selenoprotein X, 1 Oxidoreductase, Metal-binding, Zinc, 3545 7513 Selenium, Selenocysteine NM_016333 SRRM2 serine/arginine Hypothetical protein 3546 7514 repetitive matrix 2 NM_016334 SH120 putative G-protein Receptor 3547 7515 coupled receptor NM_016354 SLC21A12 solute carrier organic Transmembrane, Transport, Ion 3548 7516 anion transporter transport, Glycoprotein, Alternative family, member 4A1 splicing NM_016355 LOC51202 DEAD (Asp-Glu-Ala- ATP-binding, Helicase, Hydrolase, 3549 7517 Asp) box polypeptide Hypothetical protein 47 NM_016362 GHRL ghrelin precursor Hormone, Cleavage on pair of basic 3550 7518 residues, Signal, Lipoprotein, Alternative splicing NM_016364 DUSP13 dual specificity Hydrolase 3551 7519 phosphatase 13 NM_016373 WWOX WW domain Oxidoreductase 3552 7520 containing oxidoreductase NM_016377 AKAP7 A kinase (PRKA) Membrane, Myristate, Palmitate, 3553 7521 anchor protein 7 Lipoprotein, Alternative splicing NM_016381 TREX1 three prime repair Exonuclease, Hypothetical protein 3554 7522 exonuclease 1 NM_016385 CYLD cylindromatosis Hypothetical protein 3555 7523 (turban tumor syndrome) NM_016387 HSPC060 hypothetical protein 3556 7524 HSPC060 NM_016391 HSPC111 hypothetical protein Hypothetical protein, Nuclear protein 3557 7525 HSPC111 NM_016397 TH1L TH1-like Transcription regulation, Repressor, 3558 7526 (Drosophila) Nuclear protein, Alternative splicing, Alternative initiation NM_016399 HSPC132 hypothetical protein Hypothetical protein 3559 7527 HSPC132 NM_016403 HSPC148 hypothetical protein Hypothetical protein 3560 7528 HSPC148 NM_016407 C20orf43 chromosome 20 Alternative splicing 3561 7529 open reading frame 43 NM_016418 NF2 neurofibromin 2 Structural protein, Cytoskeleton, 3562 7530 (bilateral acoustic Anti-oncogene, Disease mutation, neuroma) Alternative splicing, Deafness, 3D- structure NM_016424 LUC7A cisplatin resistance- Phosphorylation, Hypothetical 3563 7531 associated protein overexpressed protein NM_016431 MAPK8IP2 mitogen-activated SH3 domain, Alternative splicing 3564 7532 protein kinase 8 interacting protein 2 NM_016441 CRIM1 cysteine-rich motor Signal 3565 7533 neuron 1 NM_016463 HSPC195 hypothetical protein Hypothetical protein 3566 7534 HSPC195 NM_016465 LOC51238 blocked early in Hypothetical protein 3567 7535 transport 1 homolog (S. cerevisiae) like NM_016468 C14orf112 chromosome 14 Hypothetical protein 3568 7536 open reading frame 112 NM_016477 FOXP1 forkhead box P1 Hypothetical protein, Transcription 3569 7537 regulation, DNA-binding, Zinc-finger, Metal-binding, Nuclear protein, Alternative splicing NM_016479 SCOTIN scotin Hypothetical protein 3570 7538 NM_016501 FLJ10597 hypothetical protein Hypothetical protein 3571 7539 FLJ10597 NM_016503 MRPL30 mitochondrial Hypothetical protein 3572 7540 ribosomal protein L30 NM_016507 CRK7 CDC2-related Transferase, Serine/threonine- 3573 7541 protein kinase 7 protein kinase, ATP-binding, Nuclear protein NM_016524 LOC51760 B/K protein Hypothetical protein 3574 7542 NM_016533 NINJ2 ninjurin 2 Cell adhesion, Transmembrane 3575 7543 NM_016538 SIRT7 sirtuin (silent mating Hydrolase, NAD, Metal-binding, 3576 7544 type information Zinc, Alternative splicing regulation 2 homolog) 7 (S. cerevisiae) NM_016565 E2IG2 E2IG2 protein 3577 7545 NM_016567 BCCIP BRCA2 and Helicase, Hypothetical protein 3578 7546 CDKN1A interacting protein NM_016572 USP21 ubiquitin specific Hypothetical protein, Ubl conjugation 3579 7547 protease 21 pathway, Hydrolase, Thiol protease, Multigene family NM_016573 LOC51291 Gem-interacting 3580 7548 protein NM_016574 DRD2 dopamine receptor G-protein coupled receptor, 3581 7549 D2 Transmembrane, Glycoprotein, Multigene family, Alternative splicing, Disease mutation, Polymorphism, 3D-structure NM_016582 FLJ20539 solute carrier family Hypothetical protein 3582 7550 15, member 3 NM_016594 FKBP11 FK506 binding Isomerase, Rotamase, Signal 3583 7551 protein 11, 19 kDa NM_016598 ZDHHC3 zinc finger, DHHC Transmembrane, Golgi stack, Zinc- 3584 7552 domain containing 3 finger, Alternative splicing NM_016603 C5orf5 chromosome 5 open GTPase activation 3585 7553 reading frame 5 NM_016608 ALEX1 ALEX1 protein Hypothetical protein 3586 7554 NM_016610 TLR8 toll-like receptor 8 Hypothetical protein, Receptor, 3587 7555 Immune response, Inflammatory response, Signal, Transmembrane, Repeat, Leucine-rich repeat, Glycoprotein NM_016612 MSCP mitochondrial solute Hypothetical protein 3588 7556 carrier protein NM_016616 TXNDC3 thioredoxin domain Redox-active center 3589 7557 containing 3 (spermatozoa) NM_016619 PLAC8 placenta-specific 8 3590 7558 NM_016623 BM-009 hypothetical protein Hypothetical protein 3591 7559 BM-009 NM_016626 LOC51320 hypothetical protein Metal-binding, Zinc, Zinc-finger 3592 7560 LOC51320 NM_016630 ACP33 acid cluster protein Hypothetical protein 3593 7561 33 NM_016639 TNFRSF12A tumor necrosis factor Receptor, Angiogenesis, Apoptosis, 3594 7562 receptor superfamily, Transmembrane, Signal, Alternative member 12A splicing NM_016640 MRPS30 mitochondrial Ribosomal protein, Mitochondrion 3595 7563 ribosomal protein S30 NM_016733 LIMK2 LIM domain kinase 2 Transferase, Serine/threonine- 3596 7564 protein kinase, ATP-binding, Repeat, LIM domain, Metal-binding, Zinc, Kinase, Tyrosine-protein kinase, Hypothetical protein NM_016826 OGG1 8-oxoguanine DNA Hydrolase, Nuclease, Endonuclease, 3597 7565 glycosylase Lyase, DNA repair, Glycosidase, Multifunctional enzyme, Nuclear protein, Mitochondrion, Alternative splicing, Polymorphism, 3D- structure, Transferase, Serine/threonine-protein kinase, Calmodulin-binding, Phosphorylation, NM_016827 OGG1 8-oxoguanine DNA Hydrolase, Nuclease, Endonuclease, 3598 7566 glycosylase Lyase, DNA repair, Glycosidase, Multifunctional enzyme, Nuclear protein, Mitochondrion, Alternative splicing, Polymorphism, 3D- structure, Transferase, Serine/threonine-protein kinase, Calmodulin-binding, Phosphorylation, NM_016836 RBMS1 RNA binding motif, DNA-binding, DNA replication, RNA- 3599 7567 single stranded binding, Nuclear protein, interacting protein 1 Phosphorylation NM_016839 RBMS1 RNA binding motif, DNA-binding, DNA replication, RNA- 3600 7568 single stranded binding, Nuclear protein, interacting protein 1 Phosphorylation NM_016936 UBN1 ubinuclein 1 3601 7569 NM_016951 CKLF chemokine-like Chemotaxis, Cytokine, 3602 7570 factor Transmembrane, Alternative splicing NM_017409 HOXC10 homeo box C10 Homeobox, DNA-binding, 3603 7571 Developmental protein, Nuclear protein, Transcription regulation NM_017414 USP18 ubiquitin specific Ubl conjugation pathway, Hydrolase, 3604 7572 protease 18 Thiol protease, Multigene family NM_017415 KLHL3 kelch-like 3 Cytoskeleton, Actin-binding, Kelch 3605 7573 (Drosophila) repeat, Repeat, Alternative splicing NM_017421 COQ3 coenzyme Q3 Transferase 3606 7574 homolog, methyltransferase (yeast) NM_017424 CECR1 cat eye syndrome Hydrolase, Signal, Hypothetical 3607 7575 chromosome region, protein candidate 1 NM_017426 NUP54 nucleoporin 54 kDa Hypothetical protein, Transport, 3608 7576 Nuclear protein, Repeat, Glycoprotein, Alternative splicing NM_017451 BAIAP2 BAI1-associated Receptor, SH3 domain, Hypothetical 3609 7577 protein 2 protein, ATP-binding, Transferase NM_017455 SDFR1 stromal cell derived Immunoglobulin domain, 3610 7578 factor receptor 1 Hypothetical protein, Receptor NM_017456 PSCD1 pleckstrin homology, Guanine-nucleotide releasing factor, 3611 7579 Sec7 and coiled-coil Coiled coil, Alternative splicing, 3D- domains 1(cytohesin structure 1) NM_017491 WDR1 WD repeat domain 1 Repeat, WD repeat, Hypothetical 3612 7580 protein, Actin-binding, Cytoskeleton, Alternative splicing, Polymorphism NM_017493 HSHIN1 HIV-1 induced 3613 7581 protein HIN-1 NM_017535 DKFZp566H0824 hypothetical protein Hypothetical protein 3614 7582 DKFZp566H0824 NM_017544 NRF NF-kappa B- Transcription regulation, Repressor, 3615 7583 repressing factor DNA-binding, Nuclear protein NM_017546 C40 hypothetical protein Hypothetical protein 3616 7584 C40 NM_017555 EGLN2 egl nine homolog 2 Oxidoreductase, Dioxygenase, 3617 7585 (C. elegans) Nuclear protein, Iron, Vitamin C NM_017567 NAGK N-acetylglucosamine Kinase, Transferase, ATP-binding, 3618 7586 kinase Phosphorylation, Hypothetical protein NM_017571 LOC55580 hypothetical protein Hypothetical protein 3619 7587 LOC55580 NM_017572 MKNK2 MAP kinase- Hypothetical protein, ATP-binding, 3620 7588 interacting Kinase, Serine/threonine-protein serine/threonine kinase, Transferase, Translation kinase 2 regulation, Phosphorylation, Alternative splicing NM_017596 KIAA0449 KIAA0449 protein Hypothetical protein, Repeat, WD 3621 7589 repeat NM_017622 FLJ20014 hypothetical protein Hypothetical protein 3622 7590 FLJ20014 NM_017631 FLJ20035 hypothetical protein Hypothetical protein 3623 7591 FLJ20035 NM_017633 C6orf37 chromosome 6 open Hypothetical protein 3624 7592 reading frame 37 NM_017646 IPT tRNA Hypothetical protein, Transferase 3625 7593 isopentenyltransferase 1 NM_017664 ANKRD10 ankyrin repeat Hypothetical protein, ANK repeat, 3626 7594 domain 10 Repeat NM_017681 FLJ20130 hypothetical protein Hypothetical protein, Porin 3627 7595 FLJ20130 NM_017694 FLJ20160 FLJ20160 protein Hypothetical protein 3628 7596 NM_017700 FLJ20184 hypothetical protein Hypothetical protein 3629 7597 FLJ20184 NM_017703 FBXL12 F-box and leucine- Ubl conjugation pathway, Repeat, 3630 7598 rich repeat protein Leucine-rich repeat, Alternative 12 splicing NM_017714 C20orf13 chromosome 20 Hydrolase 3631 7599 open reading frame 13 NM_017730 FLJ20259 FLJ20259 protein Hypothetical protein 3632 7600 NM_017735 FLJ20272 hypothetical protein Hypothetical protein 3633 7601 FLJ20272 NM_017737 FLJ20275 transducer of Cdc42- Hypothetical protein, SH3 domain 3634 7602 dependent actin assembly 1 NM_017740 ZDHHC7 zinc finger, DHHC Transmembrane, Zinc-finger, 3635 7603 domain containing 7 Alternative splicing NM_017742 FLJ20281 zinc finger, CCHC Hypothetical protein, Zinc-finger 3636 7604 domain containing 2 NM_017746 FLJ20287 hypothetical protein- Hypothetical protein 3637 7605 FLJ20287 NM_017756 FLJ20306 hypothetical protein Hypothetical protein 3638 7606 FLJ20306 NM_017775 FLJ20343 hypothetical protein Hypothetical protein 3639 7607 FLJ20343 NM_017785 FLJ20364 hypothetical protein Hypothetical protein 3640 7608 FLJ20364 NM_017787 FLJ20154 chromosome 10 Hypothetical protein 3641 7609 open reading frame 26 NM_017801 CKLFSF6 chemokine-like Chemotaxis, Cytokine, 3642 7610 factor super family 6 Transmembrane NM_017803 FLJ20399 hypothetical protein Hypothetical protein 3643 7611 FLJ20399 NM_017812 FLJ20420 hypothetical protein Hypothetical protein 3644 7612 FLJ20420 NM_017814 FLJ20422 hypothetical protein Hypothetical protein 3645 7613 FLJ20422 NM_017816 LYAR hypothetical protein Hypothetical protein 3646 7614 FLJ20425 NM_017817 RAB20 RAB20, member GTP-binding, Lipoprotein, 3647 7615 RAS oncogene Prenylation, Protein transport, family Polymorphism NM_017819 FLJ20432 hypothetical protein Hypothetical protein 3648 7616 FLJ20432 NM_017820 FLJ20433 hypothetical protein Hypothetical protein 3649 7617 FLJ20433 NM_017821 RHBDL2 rhomboid, veinlet- Hydrolase, Protease, Serine 3650 7618 like 2 (Drosophila) protease, Transmembrane NM_017824 FLJ20445 hypothetical protein Hypothetical protein 3651 7619 FLJ20445 NM_017836 FLJ20473 hypothetical protein Hypothetical protein 3652 7620 FLJ20473 NM_017838 NOLA2 nucleolar protein 3653 7621 family A, member 2 (H/ACA small nucleolar RNPs) NM_017840 MRPL16 mitochondrial Ribosomal protein, Hypothetical 3654 7622 ribosomal protein protein L16 NM_017844 ANKMY1 ankyrin repeat and Hypothetical protein, ANK repeat, 3655 7623 MYND domain Repeat, Zinc-finger, Alternative containing 1 splicing NM_017847 C1orf27 chromosome 1 open Hypothetical protein 3656 7624 reading frame 27 NM_017849 FLJ20507 hypothetical protein Hypothetical protein 3657 7625 FLJ20507 NM_017850 FLJ20508 hypothetical protein Hypothetical protein 3658 7626 FLJ20508 NM_017859 URKL1 uridine kinase-like 1 Transferase, Kinase, ATP-binding 3659 7627 NM_017866 FLJ20533 hypothetical protein Hypothetical protein 3660 7628 FLJ20533 NM_017874 C20orf27 chromosome 20 Hypothetical protein 3661 7629 open reading frame 27 NM_017885 FLJ20568 host cell factor C1 Hypothetical protein 3662 7630 regulator 1 (XPO1 dependant) NM_017895 DDX27 DEAD (Asp-Glu-Ala- Hydrolase, Helicase, ATP-binding, 3663 7631 Asp) box polypeptide Nuclear protein, Alternative splicing 27 NM_017899 TSC hypothetical protein Calcium-binding, Hypothetical 3664 7632 FLJ20607 protein NM_017900 FLJ20608 aurora-A kinase Hypothetical protein, Nuclear protein 3665 7633 interacting protein NM_017906 FLJ20624 PAK1 interacting Hypothetical protein, Repeat, WD 3666 7634 protein 1 repeat NM_017907 FLJ20625 hypothetical protein Hypothetical protein 3667 7635 FLJ20625 NM_017910 FLJ20628 hypothetical protein Hypothetical protein 3668 7636 FLJ20628 NM_017942 BTBD1 BTB (POZ) domain 3669 7637 containing 1 NM_017952 FLJ20758 FLJ20758 protein Hypothetical protein 3670 7638 NM_017953 FLJ20729 hypothetical protein Hypothetical protein 3671 7639 FLJ20729 NM_017956 FLJ20772 hypothetical protein Hypothetical protein 3672 7640 FLJ20772 NM_017983 KIAA1001 hypothetical protein Hypothetical protein, Repeat, WD 3673 7641 FLJ10055 repeat NM_018007 FBXO4 Homo sapiens cDNA Ubl conjugation pathway, 3674 7642 FLJ10141 fis, clone Hypothetical protein HEMBA1003199. NM_018024 FLJ10204 hypothetical protein Hypothetical protein 3675 7643 FLJ10204 NM_018044 WBSCR20A Williams Beuren Nuclear protein, Transport, 3676 7644 syndrome Transmembrane, Repeat, chromosome region Hypothetical protein 20A NM_018045 FLJ10276 hypothetical protein Hypothetical protein 3677 7645 FLJ10276 NM_018050 FLJ10298 hypothetical protein Hypothetical protein 3678 7646 FLJ10298 NM_018051 FLJ10300 hypothetical protein Hypothetical protein, Repeat, WD 3679 7647 FLJ10300 repeat NM_018053 FLJ10307 hypothetical protein Hypothetical protein 3680 7648 FLJ10307 NM_018056 FLJ10315 hypothetical protein Hypothetical protein 3681 7649 FLJ10315 NM_018059 FLJ10324 hypothetical protein Hypothetical protein 3682 7650 FLJ10324 NM_018067 FLJ10350 hypothetical protein Hypothetical protein 3683 7651 FLJ10350 NM_018075 FLJ10375 hypothetical protein Hypothetical protein 3684 7652 FLJ10375 NM_018087 FLJ10407 hypothetical protein Hypothetical protein 3685 7653 FLJ10407 NM_018089 FLJ10415 hypothetical protein Hypothetical protein, ANK repeat, 3686 7654 FLJ10415 Repeat NM_018093 FLJ10439 hypothetical protein Hypothetical protein, Repeat, WD 3687 7655 FLJ10439 repeat NM_018099 FLJ10462 hypothetical protein Hypothetical protein 3688 7656 FLJ10462 NM_018100 FLJ10466 EF-hand domain (C- Hypothetical protein 3689 7657 terminal) containing 1 NM_018113 LIMR lipocalin-interacting Hypothetical protein, Receptor 3690 7658 membrane receptor NM_018119 SIN RNA polymerase III Transferase, DNA-directed RNA 3691 7659 80 kDa subunit polymerase, Transcription, Nuclear RPC5 protein, Alternative splicing NM_018125 FLJ10521 hypothetical protein Hypothetical protein 3692 7660 FLJ10521 NM_018127 ELAC2 elaC homolog 2 (E. coli) Hypothetical protein 3693 7661 NM_018128 SRR hypothetical protein Isomerase, Pyridoxal phosphate, 3694 7662 FLJ10534 Hypothetical protein NM_018137 PRMT6 protein arginine N- Transferase, Methyltransferase, 3695 7663 methyltransferase 6 Nuclear protein, Methylation NM_018140 FLJ10565 hypothetical protein Hypothetical protein 3696 7664 FLJ10565 NM_018142 FLJ10569 hypothetical protein Hypothetical protein 3697 7665 FLJ10569 NM_018147 FAIM Fas apoptotic Apoptosis, Alternative splicing 3698 7666 inhibitory molecule NM_018158 SLC4A1AP solute carrier family Hypothetical protein, Transcription 3699 7667 4 (anion exchanger), regulation, Nuclear protein, Antigen, member 1, adaptor Alternative splicing protein NM_018161 FLJ10631 NAD synthetase 1 Hypothetical protein 3700 7668 NM_018169 FLJ10652 hypothetical protein Hypothetical protein 3701 7669 FLJ10652 NM_018170 FLJ10656 hypothetical protein Kinase, Hypothetical protein 3702 7670 FLJ10656 NM_018174 VCY2IP1 VCY2 interacting Hypothetical protein 3703 7671 protein 1 NM_018182 FLJ10700 hypothetical protein Hypothetical protein 3704 7672 FLJ10700 NM_018191 RCBTB1 regulator of Hypothetical protein 3705 7673 chromosome condensation (RCC1) and BTB (POZ) domain containing protein 1 NM_018194 FLJ10724 melanoma antigen Hypothetical protein 3706 7674 recognized by T cells 2 NM_018195 FLJ10726 hypothetical protein Hypothetical protein 3707 7675 FLJ10726 NM_018197 ZFP64 zinc finger protein 64 Transcription regulation, Zinc-finger, 3708 7676 homolog (mouse) Metal-binding, Nuclear protein, DNA- binding, Repeat, Alternative splicing NM_018203 FLJ10748 hypothetical protein Hypothetical protein 3709 7677 FLJ10748 NM_018208 FLJ10761 putative Transferase, Kinase 3710 7678 ethanolamine kinase NM_018209 ARFGAP1 ADP-ribosylation Transport, Protein transport, 3711 7679 factor GTPase GTPase activation, Golgi stack, activating protein 1 Zinc-finger, Alternative splicing, Polymorphism NM_018217 C20orf31 chromosome 20 Hydrolase, Glycosidase, 3712 7680 open reading frame Glycoprotein, Signal, Polymorphism 31 NM_018226 RNPEPL1 arginyl Aminopeptidase, Hydrolase, Zinc, 3713 7681 aminopeptidase Metalloprotease (aminopeptidase B)- like 1 NM_018235 FLJ10830 cytosolic nonspecific Hydrolase, Carboxypeptidase, 3714 7682 dipeptidase (EC Metalloprotease, Hypothetical 3.4.13.18) protein NM_018243 FLJ10849 hypothetical protein Hypothetical protein 3715 7683 FLJ10849 NM_018246 FLJ10853 hypothetical protein Hypothetical protein 3716 7684 FLJ10853 NM_018255 STATIP1 signal transducer Hypothetical protein, Repeat, WD 3717 7685 and activator of repeat transcription 3 interacting protein 1 NM_018256 WDR12 WD repeat domain Repeat, WD repeat, Polymorphism 3718 7686 12 NM_018257 C20orf36 chromosome 20 Transcription regulation, Zinc-finger, 3719 7687 open reading frame DNA-binding, Nuclear protein, 36 Repeat, Alternative splicing NM_018259 FLJ10890 hypothetical protein Hypothetical protein 3720 7688 FLJ10890 NM_018264 FLJ10900 hypothetical protein Hypothetical protein 3721 7689 FLJ10900 NM_018265 FLJ10901 hypothetical protein Hypothetical protein 3722 7690 FLJ10901 NM_018267 H2AFJ H2A histone family, Hypothetical protein 3723 7691 member J NM_018275 FLJ10925 hypothetical protein Hypothetical protein 3724 7692 FLJ10925 NM_018306 FLJ11036 hypothetical protein Hypothetical protein 3725 7693 FLJ11036 NM_018317 FLJ11082 hypothetical protein Hypothetical protein 3726 7694 FLJ11082 NM_018319 TDP1 tyrosyl-DNA Hypothetical protein, Hydrolase, 3727 7695 phosphodiesterase 1 DNA repair, Repeat, Nuclear protein, 3D-structure, Disease mutation NM_018321 RAD1 BRIX Hypothetical protein, Ribosome 3728 7696 biogenesis, Nuclear protein, Cell cycle, Exonuclease NM_018322 C6orf64 chromosome 6 open Hypothetical protein, Dynein 3729 7697 reading frame 64 NM_018324 FLJ11106 hypothetical protein Hypothetical protein 3730 7698 FLJ11106 NM_018326 HIMAP4 immunity associated GTP-binding, Coiled coil, 3731 7699 protein 4 Polymorphism NM_018332 DDX19 hypothetical protein ATP-binding, Helicase, Hydrolase, 3732 7700 FLJ11126 RNA-binding, Nuclear protein, Hypothetical protein NM_018333 FLJ20666 hypothetical protein Hypothetical protein 3733 7701 FLJ20666 NM_018358 FLJ11198 ATP-binding Hypothetical protein, ATP-binding 3734 7702 cassette, sub-family F (GCN20), member 3 NM_018359 FLJ11200 hypothetical protein Hypothetical protein 3735 7703 FLJ11200 NM_018361 FLJ11210 acid acyltransferase- Phospholipid biosynthesis, 3736 7704 epsilon Transferase, Acyltransferase, Transmembrane NM_018371 ChGn chondroitin beta1,4 Transferase, Hypothetical protein 3737 7705 N- acetylgalactosaminyl transferase NM_018373 SYNJ2BP synaptojanin 2 Mitochondrion, Outer membrane, 3738 7706 binding protein Transmembrane NM_018379 FLJ11280 hypothetical protein Hypothetical protein 3739 7707 FLJ11280 NM_018386 FLJ11305 hypothetical protein Hypothetical protein 3740 7708 FLJ11305 NM_018387 STRBP spermatid Hypothetical protein 3741 7709 perinuclear RNA binding protein NM_018391 FLJ23277 ubiquitin specific Hypothetical protein, Protease 3742 7710 protease 31 NM_018394 FLJ11342 hypothetical protein Hypothetical protein 3743 7711 FLJ11342 NM_018399 VNN3 vanin 3 Hydrolase, Signal, Glycoprotein, 3744 7712 GPI-anchor, Lipoprotein NM_018403 HSA275986 transcription factor Hypothetical protein 3745 7713 SMIF NM_018404 CENTA2 centaurin, alpha 2 GTPase activation, Repeat, Zinc- 3746 7714 finger NM_018407 LAPTM4B lysosomal 3747 7715 associated protein transmembrane 4 beta NM_018421 TBC1D2 TBC1 domain family, Hypothetical protein, GTPase 3748 7716 member 2 activation, Antigen NM_018422 DKFZp761K1423 hypothetical protein Hypothetical protein 3749 7717 DKFZp761K1423 NM_018423 DKFZp761p1010 protein kinase ATP-binding, Kinase, Receptor, 3750 7718 STYK1 Transferase, Tyrosine-protein kinase, Hypothetical protein NM_018441 PECR peroxisomal trans 2- Oxidoreductase 3751 7719 enoyl CoA reductase NM_018443 ZNF302 zinc finger protein Hypothetical protein, Metal-binding, 3752 7720 302 Zinc, Zinc-finger, Transcription regulation, DNA-binding, Nuclear protein, Repeat, Alternative splicing NM_018449 UBAP2 ubiquitin associated Hypothetical protein 3753 7721 protein 2 NM_018452 C6orf35 chromosome 6 open Hypothetical protein 3754 7722 reading frame 35 NM_018457 DKFZP564J157 DKFZp564J157 Hypothetical protein 3755 7723 protein NM_018465 MDS030 chromosome 9 open Hypothetical protein 3756 7724 reading frame 46 NM_018472 HT011 uncharacterized Hypothetical protein 3757 7725 hypothalamus protein HT011 NM_018480 HT007 uncharacterized Hypothetical protein 3758 7726 hypothalamus protein HT007 NM_018485 GPR77 G protein-coupled G-protein coupled receptor, 3759 7727 receptor 77 Transmembrane, Glycoprotein NM_018486 HDAC8 histone deacetylase 8 Hydrolase, Nuclear protein, 3760 7728 Chromatin regulator, Transcription regulation, Repressor, Alternative splicing NM_018491 LOC55871 COBW-like protein Hypothetical protein 3761 7729 NM_018515 PRO2176 EST, Highly similar 3762 7730 to hypothetical protein PRO2176 [Homo sapiens] [H. sapiens] NM_018520 PRO2268 hypothetical protein 3763 7731 PRO2268 NM_018533 RAB7 Homo sapiens cDNA GTP-binding, Lipoprotein, 3764 7732 FLJ20819 fis, clone Prenylation, Protein transport, ADSE00511. Hypothetical protein NM_018556 SIRPB2 signal-regulatory Repeat, Signal, Transmembrane, 3765 7733 protein beta 2 Immunoglobulin domain, Glycoprotein, Alternative splicing NM_018569 PRO0971 hypothetical protein Hypothetical protein 3766 7734 PRO0971 NM_018572 PRO1051 E2F transcription 3767 7735 factor 3 NM_018590 PRO0082 chondroitin sulfate Hypothetical protein, Transferase 3768 7736 GalNAcT-2 NM_018594 PRO0823 FYN binding protein SH3 domain, Phosphorylation, 3769 7737 (FYB-120/130) Nuclear protein, Coiled coil, Alternative splicing NM_018615 PRO2032 Homo sapiens 3770 7738 hypothetical protein PRO2032 (PRO2032), mRNA. NM_018638 EKI1 ethanolamine kinase Transferase, Kinase 3771 7739 NM_018643 TREM1 triggering receptor Receptor 3772 7740 expressed on myeloid cells 1 NM_018648 NOLA3 nucleolar protein 3773 7741 family A, member 3 (H/ACA small nucleolar RNPs) NM_018676 THSD1 thrombospondin, Signal 3774 7742 type I, domain 1 NM_018687 LOC55908 hepatocellular 3775 7743 carcinoma- associated gene TD26 NM_018688 BIN3 bridging integrator 3 Septation, Cytoskeleton, Coiled coil, 3776 7744 Hypothetical protein NM_018690 APOB48R apolipoprotein B48 Hypothetical protein, Lipoprotein, 3777 7745 receptor Receptor NM_018699 PRDM5 PR domain Transcription regulation, DNA- 3778 7746 containing 5 binding, Zinc-finger, Metal-binding, Nuclear protein, Repeat NM_018728 MYO5C myosin VC Myosin, Repeat, ATP-binding, 3779 7747 Calmodulin-binding, Actin-binding, Coiled coil, Polymorphism NM_018834 MATR3 matrin 3 Nuclear protein, RNA-binding, 3780 7748 Repeat, Zinc-finger NM_018839 NSFL1C NSFL1 (p97) Hypothetical protein 3781 7749 cofactor (p47) NM_018840 C20orf24 chromosome 20 Alternative splicing, Membrane, SH2 3782 7750 open reading frame domain, SH3 domain, Myristate, 24 Phosphorylation, Alternative initiation, Lipoprotein NM_018939 PCDHB6 protocadherin beta 6 Calcium-binding, Cell adhesion, 3783 7751 Glycoprotein, Signal, Repeat, Transmembrane, Multigene family NM_018959 DAZAP1 DAZ associated Hypothetical protein 3784 7752 protein 1 NM_018961 UBASH3A ubiquitin associated Nuclear protein, SH3 domain, 3785 7753 and SH3 domain Alternative splicing containing, A NM_018983 NOLA1 nucleolar protein 3786 7754 family A, member 1 (H/ACA small nucleolar RNPs) NM_018996 FLJ20015 KIAA1582 protein Hypothetical protein 3787 7755 NM_019002 ETAA16 ETAA16 protein 3788 7756 NM_019009 TOLLIP toll interacting Hypothetical protein, Immune 3789 7757 protein response, Inflammatory response NM_019012 PEPP2 phosphoinositol 3- Hypothetical protein 3790 7758 phosphate-binding protein-2 NM_019018 FLJ11127 hypothetical protein Hypothetical protein 3791 7759 FLJ11127 NM_019042 FLJ20485 hypothetical protein Hypothetical protein, tRNA 3792 7760 FLJ20485 processing, Lyase NM_019057 FLJ10404 hypothetical protein Hypothetical protein 3793 7761 FLJ10404 NM_019063 EML4 echinoderm Microtubule, Repeat, WD repeat, 3794 7762 microtubule Hypothetical protein associated-protein like 4 NM_019067 FLJ10613 hypothetical protein Hypothetical protein 3795 7763 FLJ10613 NM_019084 FLJ10895 hypothetical protein Hypothetical protein 3796 7764 FLJ10895 NM_019096 GTPBP2 GTP binding protein 2 GTP-binding, Protein biosynthesis, 3797 7765 Hypothetical protein NM_019112 ABCA7 ATP-binding ATP-binding, Hypothetical protein 3798 7766 cassette, sub-family A (ABC1), member 7 NM_019554 S100A4 S100 calcium Calcium-binding, 3D-structure 3799 7767 binding protein A4 (calcium protein, calvasculin, metastasin, murine placental homolog) NM_019604 CRTAM class-I MHC- 3800 7768 restricted T cell associated molecule NM_019848 P3 solute carrier family Transmembrane, Transport, 3801 7769 10 (sodium/bile acid Symport cotransporter family), member 3 NM_019892 PPI5PIV inositol 3802 7770 polyphosphate-5- phosphatase, 72 kDa NM_019896 POLE4 polymerase (DNA- DNA-directed DNA polymerase, 3803 7771 directed), epsilon 4 DNA-binding, Nuclear protein (p12 subunit) NM_020038 ABCC3 ATP-binding ATP-binding, Glycoprotein, 3804 7772 cassette, sub-family Transmembrane, Transport, Repeat, C (CFTR/MRP), Alternative splicing member 3 NM_020123 SMBP SM-11044 binding Hypothetical protein, Signal, 3805 7773 protein Transmembrane NM_020133 LPAAT- 1-acylglycerol-3- Phospholipid biosynthesis, 3806 7774 delta phosphate O- Transferase, Acyltransferase, acyltransferase 4 Transmembrane (lysophosphatidic acid acyltransferase, delta) NM_020134 DPYSL5 dihydropyrimidinase- Hypothetical protein 3807 7775 like 5 NM_020135 WHIP Werner helicase ATP-binding, Helicase, Hypothetical 3808 7776 interacting protein 1 protein NM_020139 LOC56898 dehydrogenase/reductase Oxidoreductase, Hypothetical protein 3809 7777 (SDR family) member 6 NM_020143 LOC56902 putatative 28 kDa Hypothetical protein 3810 7778 protein NM_020149 MEIS2 Meis1, myeloid Hypothetical protein, Homeobox, 3811 7779 ecotropic viral DNA-binding, Nuclear protein, integration site 1 Alternative splicing homolog 2 (mouse) NM_020152 C21orf7 chromosome 21 Alternative splicing, Hypothetical 3812 7780 open reading frame 7 protein NM_020158 RRP46 exosome component Exosome, Hydrolase, Nuclease, 3813 7781 Rrp46 Exonuclease, rRNA processing, Nuclear protein, RNA-binding, Antigen NM_020166 MCCC1 methylcrotonoyl- Mitochondrion, Ligase, Biotin, ATP- 3814 7782 Coenzyme A binding, Transit peptide, Disease carboxylase 1 mutation, Polymorphism (alpha) NM_020179 FN5 FN5 protein 3815 7783 NM_020184 CNNM4 cyclin M4 Hypothetical protein 3816 7784 NM_020188 DC13 DC13 protein 3817 7785 NM_020193 C11ORF30 chromosome 11 Hypothetical protein 3818 7786 open reading frame 30 NM_020198 GK001 GK001 protein Hypothetical protein 3819 7787 NM_020200 HHGP phosphoribosyl Transferase 3820 7788 transferase domain containing 1 NM_020201 NT5M 5′,3′-nucleotidase, Nucleotide metabolism, Hydrolase, 3821 7789 mitochondrial Mitochondrion, Nucleotide-binding, Magnesium, Transit peptide, 3D- structure NM_020216 RNPEP arginyl Aminopeptidase, Hydrolase, Zinc, 3822 7790 aminopeptidase Metalloprotease (aminopeptidase B) NM_020229 PRDM11 PR domain Hypothetical protein 3823 7791 containing 11 NM_020231 MDS010 x 010 protein Hypothetical protein 3824 7792 NM_020234 MDS009 x 009 protein Hypothetical protein 3825 7793 NM_020236 MRPL1 mitochondrial Hypothetical protein, Ribosomal 3826 7794 ribosomal protein L1 protein NM_020239 SPEC1 small protein effector Hypothetical protein 3827 7795 1 of Cdc42 NM_020243 TOMM22 translocase of outer Receptor, Translocation, Transport, 3828 7796 mitochondrial Protein transport, Outer membrane, membrane 22 Mitochondrion, Transmembrane homolog (yeast) NM_020313 LOC57019 hypothetical protein Hypothetical protein 3829 7797 LOC57019 NM_020314 MGC16824 esophageal cancer Hypothetical protein 3830 7798 associated protein NM_020322 ACCN3 amiloride-sensitive Ionic channel 3831 7799 cation channel 3 NM_020344 SLC24A2 solute carrier family Vision, Transport, Antiport, Symport, 3832 7800 24 Calcium transport, Potassium (sodium/potassium/calcium transport, Sodium transport, exchanger), Transmembrane, Glycoprotein, member 2 Signal, Repeat, Alternative splicing NM_020347 LZTFL1 leucine zipper 3833 7801 transcription factor- like 1 NM_020350 AGTRAP angiotensin II Receptor 3834 7802 receptor-associated protein NM_020357 PCNP PEST-containing Nuclear protein 3835 7803 nuclear protein NM_020360 PLSCR3 phospholipid Hypothetical protein, 3836 7804 scramblase 3 Transmembrane, Lipoprotein, Calcium-binding, SH3-binding, Repeat, Phosphorylation, Palmitate, Polymorphism NM_020365 EIF2B3 eukaryotic Initiation factor, Protein biosynthesis, 3837 7805 translation initiation Alternative splicing, Disease factor 2B, subunit 3 mutation, Hypothetical protein gamma, 58 kDa NM_020366 RPGRIP1 retinitis pigmentosa 3838 7806 GTPase regulator interacting protein 1 NM_020370 GPR84 G protein-coupled Receptor 3839 7807 receptor 84 NM_020371 AVEN apoptosis, caspase Apoptosis 3840 7808 activation inhibitor NM_020385 XPMC2H XPMC2 prevents Hypothetical protein 3841 7809 mitotic catastrophe 2 homolog (Xenopus laevis) NM_020390 EIF5A2 eukaryotic Initiation factor, Hypothetical protein 3842 7810 translation initiation factor 5A2 NM_020394 LOC57116 zinc finger protein Metal-binding, Zinc, Zinc-finger 3843 7811 SBZF3 NM_020399 PIST golgi associated Hypothetical protein 3844 7812 PDZ and coiled-coil motif containing NM_020401 NUP107 nuclear pore Nuclear protein, Transport 3845 7813 complex protein NM_020406 PRV1 polycythemia rubra Signal, Receptor 3846 7814 vera 1 NM_020408 CGI-203 chromosome 6 open Hypothetical protein 3847 7815 reading frame 149 NM_020410 CGI-152 cation-transporting Hydrolase, Transmembrane, 3848 7816 ATPase Phosphorylation, Magnesium, ATP- binding, Alternative splicing, Hypothetical protein NM_020414 DDX24 DEAD (Asp-Glu-Ala- Hydrolase, Helicase, ATP-binding, 3849 7817 Asp) box polypeptide RNA-binding 24 NM_020415 RETN resistin Hormone, Signal, Diabetes mellitus, 3850 7818 Obesity NM_020466 DJ122O8.2 hypothetical protein Hypothetical protein 3851 7819 dJ122O8.2 NM_020469 ABO ABO blood group Transferase, Glycosyltransferase, 3852 7820 (transferase A, alpha Blood group antigen, Golgi stack, 1-3-N- Metal-binding, Manganese, Signal- acetylgalactosaminyl anchor, Transmembrane, transferase; Glycoprotein, Polymorphism, 3D- transferase B, alpha structure 1-3- galactosyltransferase) NM_020480 ANK1 ankyrin 1, ANK repeat, Repeat, Cytoskeleton, 3853 7821 erythrocytic Alternative splicing, Phosphorylation, Lipoprotein, Disease mutation, Elliptocytosis, Polymorphism NM_020484 AF011757 Homo sapiens 3854 7822 RAGE binding protein (AF011757), mRNA. NM_020530 OSM oncostatin M Growth regulation, Cytokine, 3855 7823 Glycoprotein, Signal, 3D-structure NM_020533 MCOLN1 mucolipin 1 Hypothetical protein, Ionic channel, 3856 7824 Transmembrane NM_020548 DBI diazepam binding Transport, Lipid-binding, Acetylation, 3857 7825 inhibitor (GABA Alternative splicing receptor modulator, acyl-Coenzyme A binding protein) NM_020632 ATP6V0A4 ATPase, H+ Hydrogen ion transport, 3858 7826 transporting, Transmembrane, Glycoprotein, lysosomal V0 Disease mutation, Hypothetical subunit a isoform 4 protein NM_020639 ANKRD3 ankyrin repeat ANK repeat, Repeat, Hypothetical 3859 7827 domain 3 protein, ATP-binding, Kinase, Serine/threonine-protein kinase, Transferase, Alternative splicing NM_020648 TWSG1 twisted gastrulation Hypothetical protein, Signal 3860 7828 homolog 1 (Drosophila) NM_020652 ZNF286 zinc finger protein Transcription regulation, Zinc-finger, 3861 7829 286 Metal-binding, Nuclear protein, DNA- binding, Repeat NM_020659 TTYH1 tweety homolog 1 3862 7830 (Drosophila) NM_020664 DECR2 2,4-dienoyl CoA Hypothetical protein, Oxidoreductase 3863 7831 reductase 2, peroxisomal NM_020686 NPD009 4-aminobutyrate 3864 7832 aminotransferase NM_020905 RDH14 retinol Oxidoreductase, NADP 3865 7833 dehydrogenase 14 (all-trans and 9-cis) NM_020980 AQP9 aquaporin 9 Transport, Repeat, Transmembrane 3866 7834 NM_020983 ADCY6 adenylate cyclase 6 Lyase, cAMP biosynthesis, 3867 7835 Transmembrane, Glycoprotein, Repeat, Metal-binding, Magnesium, Alternative splicing NM_020995 HPR haptoglobin-related Hydrolase, Protease, Serine 3868 7836 protein protease NM_020999 NEUROG3 neurogenin 3 3869 7837 NM_021018 HIST1H3F histone 1, H3f Nuclear protein, Chromosomal 3870 7838 protein, DNA-binding, Nucleosome core, Multigene family, Acetylation, Methylation NM_021019 MYL6 myosin, light Myosin, Muscle protein, Acetylation, 3871 7839 polypeptide 6, alkali, Alternative splicing, Multigene family smooth muscle and non-muscle NM_021025 TLX3 T-cell leukemia, Homeobox, DNA-binding, Nuclear 3872 7840 homeobox 3 protein, Developmental protein NM_021031 CYCL Homo sapiens Hypothetical protein 3873 7841 cytochrome c-like antigen (CYCL), mRNA NM_021039 S100A14 S100 calcium Transcription regulation, DNA- 3874 7842 binding protein A14 binding, Nuclear protein, (calgizzarin) Hypothetical protein, Calcium- binding NM_021074 NDUFV2 NADH Oxidoreductase, NAD, Ubiquinone, 3875 7843 dehydrogenase Mitochondrion, Transit peptide, (ubiquinone) Metal-binding, Iron-sulfur, Iron, 2Fe—2S, flavoprotein 2, Polymorphism 24 kDa NM_021075 NDUFV3 NADH Hypothetical protein 3876 7844 dehydrogenase (ubiquinone) flavoprotein 3, 10 kDa NM_021078 GCN5L2 GCN5 general Transcription regulation, 3877 7845 control of amino-acid Transferase, Nuclear protein, synthesis 5-like 2 Bromodomain, Alternative splicing, (yeast) 3D-structure NM_021079 NMT1 N- Acyltransferase, Transferase, 3878 7846 myristoyltransferase 1 Alternative splicing NM_021090 MTMR3 myotubularin related Hydrolase, Zinc-finger, Alternative 3879 7847 protein 3 splicing NM_021103 TMSB10 thymosin, beta 10 Actin-binding, Cytoskeleton, 3880 7848 Acetylation NM_021106 RGS3 regulator of G- Hypothetical protein, Signal 3881 7849 protein signalling 3 transduction inhibitor, Alternative splicing, Phosphorylation NM_021131 PPP2R4 protein phosphatase Alternative splicing 3882 7850 2A, regulatory subunit B′ (PR 53) NM_021173 POLD4 polymerase (DNA- DNA-directed DNA polymerase, 3883 7851 directed), delta 4 DNA replication, Nuclear protein NM_021178 HEI10 chromosome 14 Ubl conjugation pathway, Ligase, 3884 7852 open reading frame Nuclear protein, Metal-binding, Zinc, 18 Coiled coil, Zinc-finger, Phosphorylation, Ubl conjugation NM_021197 WFDC1 WAP four-disulfide Serine protease inhibitor, Signal 3885 7853 core domain 1 NM_021198 NLI-IF CTD (carboxy- Hypothetical protein, Nuclear protein 3886 7854 terminal domain, RNA polymerase II, polypeptide A) small phosphatase 1 NM_021199 SQRDL sulfide quinone Oxidoreductase, Flavoprotein, FAD, 3887 7855 reductase-like NADP, Mitochondrion, Transit (yeast) peptide, Polymorphism NM_021212 ZF HCF-binding DNA-binding, Nuclear protein 3888 7856 transcription factor Zhangfei NM_021238 TERA TERA protein Hypothetical protein 3889 7857 NM_021242 STRAIT11499 MID1 interacting Hypothetical protein 3890 7858 G12-like protein NM_021251 CAPN10 calpain 10 Hydrolase, Thiol protease, Repeat, 3891 7859 Alternative splicing, Polymorphism, Diabetes mellitus NM_021259 TMEM8 transmembrane Cell adhesion, Signal, 3892 7860 protein 8 (five Transmembrane, EGF-like domain, membrane-spanning Glycoprotein domains) S73288 small small proline-rich 3893 7861 proline-rich protein 1A protein SPRK S74639 IGHM Clone I50 Immunoglobulin domain, 3894 7862 immunoglobulin Immunoglobulin C region, heavy chain variable Glycoprotein, Repeat, Pyrrolidone region mRNA, partial carboxylic acid, Polymorphism, cds Membrane, Hypothetical protein, Receptor, T-cell, Signal S77356 ATP5O ATP synthase, H+ Hydrolase, ATP synthesis, CF(1), 3895 7863 transporting, Hydrogen ion transport, mitochondrial F1 Mitochondrion, Transit peptide, complex, O subunit Polymorphism (oligomycin sensitivity conferring protein) S80864 cytochrome cytochrome c-like Hypothetical protein 3896 7864 c-like antigen polypeptide S90469 POR P450 (cytochrome) Oxidoreductase, Flavoprotein, FMN, 3897 7865 oxidoreductase FAD, NADP, Endoplasmic reticulum, Membrane, Acetylation, Polymorphism, 3D-structure U00946 KIAA0344 protein kinase, lysine Hypothetical protein, ATP-binding, 3898 7866 deficient 1 Kinase, Serine/threonine-protein kinase, Transferase U01147 ABR active BCR-related Guanine-nucleotide releasing factor, 3899 7867 gene Alternative splicing U02032 RPL23A ribosomal protein Ribosomal protein, rRNA-binding 3900 7868 L23a U09196 POLD4 polymerase (DNA- DNA-directed DNA polymerase, 3901 7869 directed), delta 4 DNA replication, Nuclear protein U14383 MUC8 Human mucin 3902 7870 (MUC8) mRNA, partial cds. U20180 IREB2 iron-responsive Iron-sulfur, 4Fe—4S, RNA-binding, 3903 7871 element binding Hypothetical protein protein 2 U25750 hypothetical protein Hypothetical protein 3904 7872 MGC20235 U36759 PTCRA pre T-cell antigen 3905 7873 receptor alpha U37689 POLR2H polymerase (RNA) II Transferase, DNA-directed RNA 3906 7874 (DNA directed) polymerase, Transcription, Nuclear polypeptide H protein U41387 DDX21 DEAD (Asp-Glu-Ala- Helicase, RNA-binding, ATP-binding, 3907 7875 Asp) box polypeptide Nuclear protein, Antigen, Repeat 21 U43431 TOP3A topoisomerase Isomerase, Topoisomerase, DNA- 3908 7876 (DNA) III alpha binding, Repeat, Zinc-finger, Alternative splicing, Polymorphism U43604 Human unidentified 3909 7877 mRNA, partial sequence. U56725 HSPA2 Human heat shock ATP-binding, Chaperone, Heat 3910 7878 protein mRNA, shock, Multigene family complete cds. U58033 MTMR2 myotubularin related Hydrolase, Charcot-Marie-Tooth 3911 7879 protein 2 disease U64205 MARK3 MAP/microtubule Transferase, Serine/threonine- 3912 7880 affinity-regulating protein kinase, ATP-binding, kinase 3 Alternative splicing, Plasmid U66702 PTPRN2 protein tyrosine Hypothetical protein, Hydrolase, 3913 7881 phosphatase, Receptor, Glycoprotein, Signal, receptor type, N Transmembrane, Diabetes mellitus, polypeptide 2 Alternative splicing U68382 MAN2B1 mannosidase, alpha, Glycosidase, Hydrolase, 3914 7882 class 2B, member 1 Glycoprotein, Lysosome, Zymogen, Signal, Disease mutation, Polymorphism U68494 solute carrier family 3915 7883 30 (zinc transporter), member 1 U69127 FUBP3 far upstream Transcription regulation, Transacting 3916 7884 element (FUSE) factor, Nuclear protein, DNA- binding protein 3 binding, Repeat, Alternative splicing U69645 ZNF32 zinc finger protein 32 Hypothetical protein, Metal-binding, 3917 7885 (KOX 30) Zinc, Zinc-finger, Transcription regulation, DNA-binding, Nuclear protein, Repeat U72882 IFI35 interferon-induced Interferon induction, Alternative 3918 7886 protein 35 splicing U79246 DIS3 FLJ22624 protein Hypothetical protein 3919 7887 U79260 MGC5149 fatso Hypothetical protein 3920 7888 U79277 tyrosine 3- Neurone, Phosphorylation, 3921 7889 monooxygenase/tryptophan Acetylation, Multigene family, 3D- 5- structure monooxygenase activation protein, zeta polypeptide U79280 PIPPIN RNA-binding protein Hypothetical protein, mRNA 3922 7890 pippin processing, RNA-binding, Nuclear protein U79282 hypothetical protein Hypothetical protein 3923 7891 LOC137886 U79290 Human clone 23908 3924 7892 mRNA sequence U79298 MGC39325 hypothetical protein Hypothetical protein 3925 7893 MGC39325 U79458 WBP2 Human WW domain Hypothetical protein 3926 7894 binding protein-2 mRNA, complete cds. U80628 TK2 thymidine kinase 2, Kinase, Transferase, DNA synthesis, 3927 7895 mitochondrial ATP-binding, Mitochondrion, Transit peptide, Alternative splicing U82277 LILRA2 leukocyte Immune response, Receptor, 3928 7896 immunoglobulin-like Repeat, Signal, Transmembrane, receptor, subfamily Immunoglobulin domain, B (with TM and ITIM Glycoprotein, Antigen, Alternative domains), member 1 splicing, Polymorphism, Multigene family, Phosphorylation, 3D-structure U83115 AIM1 absent in melanoma 1 Repeat, Lectin 3929 7897 U90878 PDLIM1 PDZ and LIM Cytoskeleton, LIM domain, Metal- 3930 7898 domain 1 (elfin) binding, Zinc U90909 MISS chromosome 14 Hypothetical protein 3931 7899 open reading frame 32 U90911 WIRE WIRE protein 3932 7900 U90916 sortilin-related Endocytosis, Receptor, 3933 7901 receptor, L(DLR Transmembrane, EGF-like domain, class) A repeats- Repeat, Glycoprotein, LDL, Lipid containing transport, Cholesterol metabolism, Signal W61000_RC NORE1 Ras association Hypothetical protein 3934 7902 (RalGDS/AF-6) domain family 5 X00437 IGHM Human mRNA for T- Immunoglobulin domain, 3935 7903 cell specific protein. Immunoglobulin C region, Glycoprotein, Repeat, Pyrrolidone carboxylic acid, Polymorphism, Membrane, Hypothetical protein, Receptor, T-cell, Signal X04201 TPM3 tropomyosin 3 Hypothetical protein, Muscle protein, 3936 7904 Cytoskeleton, Actin-binding, Coiled coil, Alternative splicing, Multigene family, Disease mutation X04526 GNB1 Human liver mRNA Transducer, Repeat, WD repeat, 3937 7905 for beta-subunit Multigene family, 3D-structure signal transducing proteins Gs/Gi (beta- G). X07618 CYP2D6 cytochrome P450, Heme, Monooxygenase, 3938 7906 family 2, subfamily Oxidoreductase, Electron transport, D, polypeptide 6 Membrane, Microsome, Endoplasmic reticulum, Polymorphism X13956 MGC10471 hypothetical protein 3939 7907 MGC10471 X15183 HSPCA heat shock 90 kDa Heat shock, Chaperone, ATP- 3940 7908 protein 1, alpha binding, Phosphorylation, 3D structure, Hypothetical protein, Plasmid X51630 WT1 Wilms tumor 1 Zinc-finger, Metal-binding, DNA- 3941 7909 binding, Repeat, Nuclear protein, Transcription regulation, Alternative splicing, Anti-oncogene, Disease mutation, Chromosomal translocation, 3D-structure X52015 IL1RN interleukin 1 receptor Glycoprotein, Signal, Alternative 3942 7910 antagonist splicing, 3D-structure X52882 TCP1 t-complex 1 Chaperone, ATP-binding, Multigene 3943 7911 family X56789 TTS-2.2 transport-secretion Hypothetical protein 3944 7912 protein 2.2 X57352 IFITM3 interferon induced Interferon induction, 3945 7913 transmembrane Transmembrane protein 3 (1-8 U) X58536 HLA-C major Glycoprotein, Signal, 3946 7914 histocompatibility Transmembrane, Hypothetical complex, class I, C protein, MHC, MHC I, Polymorphism, 3D-structure, Alternative splicing X58794 AZU1 azurocidin 1 Serine protease homolog, 3947 7915 (cationic Glycoprotein, Chemotaxis, Antibiotic, antimicrobial protein Heparin-binding, Signal, 3D- 37) structure X59417 PSMA6 proteasome Proteasome, Hydrolase, Protease, 3948 7916 (prosome, Threonine protease macropain) subunit, alpha type, 6 X61079 IGHM T cell receptor Immunoglobulin domain, 3949 7917 alpha-chain (TCR Immunoglobulin C region, Valpha20Jalpha9.14) Glycoprotein, Repeat, Pyrrolidone mRNA, partial cds. carboxylic acid, Polymorphism, Membrane, Hypothetical protein, Receptor, T-cell, Signal X62535 DGKA diacylglycerol Hypothetical protein, Kinase, 3950 7918 kinase, alpha 80 kDa Transferase, Calcium-binding, Phorbol-ester binding, Repeat, Multigene family X63417 IRLB c-myc promoter- DNA-binding, Hypothetical protein 3951 7919 binding protein X69115 ZNF37A zinc finger protein Hypothetical protein, Metal-binding, 3952 7920 37a (KOX 21) Nuclear protein, Zinc, Zinc-finger, Transcription regulation, DNA- binding, Repeat X71490 ATP6V0D1 H. sapiens mRNA for Hydrolase, ATP synthesis, Hydrogen 3953 7921 vacuolar proton ion transport ATPase, subunit D. X78817 ARHGAP4 Rho GTPase GTPase activation, SH3 domain, 3954 7922 activating protein 4 Coiled coil X87949 HSPA5 heat shock 70 kDa ATP-binding, Endoplasmic reticulum, 3955 7923 protein 5 (glucose- Signal regulated protein, 78 kDa) X89214 hpr H. sapiens mRNA for Hydrolase, Protease, Serine 3956 7924 haptoglobin related protease protein. X94232 MAPRE2 microtubule- T-cell 3957 7925 associated protein, RP/EB family, member 2 X98258 MPHOSPH9 M-phase Phosphorylation, Golgi stack, 3958 7926 phosphoprotein 9 Membrane, Coiled coil X98261 ZWINTAS ZW10 interactor Phosphorylation, Nuclear protein, 3959 7927 Coiled coil X98411 MYO1F myosin IF Myosin, ATP-binding, Actin-binding, 3960 7928 Calmodulin-binding, SH3 domain, Multigene family Y00433 GPX1 glutathione Oxidoreductase, Peroxidase, 3961 7929 peroxidase 1 Selenium, Selenocysteine, Erythrocyte, Polymorphism, Hypothetical protein Y00816 CR1 complement Complement pathway, Glycoprotein, 3962 7930 component (3b/4b) Transmembrane, Repeat, Signal, receptor 1, including Receptor, Sushi, Blood group Knops blood group antigen, Polymorphism, Pyrrolidone system carboxylic acid, 3D-structure Y14442 OR1F1 olfactory receptor, G-protein coupled receptor, 3963 7931 family 1, subfamily Transmembrane, Glycoprotein, F, member 1 Multigene family, Olfaction Y18490 LST1 leukocyte specific Immune response, Cell shape, 3964 7932 transcript 1 Transmembrane, Alternative splicing Z15114 PRKCG protein kinase C, Transferase, Serine/threonine- 3965 7933 gamma protein kinase, ATP-binding, Calcium-binding, Metal-binding, Zinc, Repeat, Phorbol-ester binding, Phosphorylation, Polymorphism Z34893 IGHM Clone P2-114 anti- Immunoglobulin domain, 3966 7934 oxidized LDL Immunoglobulin C region, immunoglobulin Glycoprotein, Repeat, Pyrrolidone heavy chain Fab carboxylic acid, Polymorphism, mRNA, partial cds Membrane, Hypothetical protein, Receptor, T-cell, Signal Z48314 MUC5AC mucin 5, subtypes A Repeat, Glycoprotein, Signal, 3967 7935 and C, Polymorphism, Hypothetical protein tracheobronchial/gastric Z49105 SSX2 synovial sarcoma, X Chromosomal translocation, Proto- 3968 7936 breakpoint 2 oncogene, Multigene family, Transcription regulation

7. REFERENCES CITED

All references cited herein are incorporated herein by reference in their entirety and for all purposes to the same extent as if each individual publication or patent or patent application was specifically and individually indicated to be incorporated by reference in its entirety for all purposes.

Many modifications and variations of the present invention can be made without departing from its spirit and scope, as will be apparent to those skilled in the art. The specific embodiments described herein are offered by way of example only, and the invention is to be limited only by the terms of the appended claims along with the full scope of equivalents to which such claims are entitled. 

1. A computer-implemented method for determining progression of chronic myeloid leukemia (CML) in a CML patient, comprising: (a) classifying, on a computer, a marker profile comprising measurements of a plurality of gene products in a cell sample taken from said patient as a chronic phase (CP-CML) profile or as an advanced phase (ADV-CML) profile, wherein said gene products are respectively products of at least 5 of the genes listed in Table 1a; (b) determining said patient as in a chronic phase if said marker profile is classified as a CP-CML profile, or determining said patient as in an advanced phase if said marker profile is classified as an ADV-CML profile; and (c) outputting to a user, a user interface device, a monitor, a computer readable storage medium, a local computer, or a computer that is part of a network; or displaying; the determination resulting from step (b).
 2. The method of claim 1, wherein said plurality of gene products further comprises a gene from Table 1b.
 3. The method of claim 1, further comprising obtaining said marker profile by a method comprising measuring said plurality of gene products in a cell sample taken from said patient.
 4. The method of claim 3, wherein said cell sample is a sample selected from the group consisting of bone marrow sample and peripheral blood sample.
 5. The method of claim 1, wherein said classifying is carried out using a progression classifier, wherein said progression classifier receives an input comprising said marker profile and provides an output comprising data indicating whether said marker profile is a CP-CML profile or an ADV-CML profile.
 6. The method of claim 5, wherein said step of classifying is carried out by a method comprising (i) comparing said marker profile with a CP-CML template profile and/or a ADV-CML said template profile, wherein said CP-CML template profile and/or said ADV-CML template profile is obtained from a training population comprising CML patients of the CP-CML and ADV-CML stage, respectively; and (ii) classifying said marker profile as a CP-CML profile if said marker profile has a high similarity to said CP-CML template profile and/or has a low similarity to said ADV-CML template profile, or classifying said marker profile as a ADV-CML profile if said marker profile has a high similarity to said ADV-CML template profile and/or has a low similarity to said CP-CML template profile, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.
 7. The method of claim 6, wherein said step of classifying is carried out by a method comprising (i) comparing said marker profile with said CP-CML template profile or said ADV-CML template profile; and (ii) classifying said marker profile as a CP-CML profile if said marker profile has a high similarity to said CP-CML template profile or has a low similarity to said ADV-CML template profile, or classifying said marker profile as a ADV-CML profile if said marker profile has a high similarity to said ADV-CML template profile or has a low similarity to said CP-CML template profile, wherein a high similarity corresponds to a degree of similarity above a predetermined threshold, and wherein a low similarity corresponds to a degree of similarity no greater than said predetermined threshold.
 8. The method of claim 6, wherein said step of classifying is carried out by a method comprising (i) comparing said marker profile with said CP-CML template profile and said ADV-CML template profile; and (ii) classifying said marker profile as a CP-CML profile if said marker profile has a higher similarity to said CP-CML template profile than to said ADV-CML template profile, or classifying said marker profile as a ADV-CML profile if said marker profile has a higher similarity to said ADV-CML template profile than to said CP-CML template profile.
 9. The method of claim 5, wherein said progression classifier is an artificial neural network (ANN) or a support vector machine (SVM).
 10. The method of claim 1, wherein said gene products are products of at least 10 of the genes listed in Table 1a.
 11. The method of claim 1, wherein said gene products further comprise products of at least 5 of the genes listed in Table
 3. 12. The method of claim 11, wherein said gene products further comprise products of at least 5 up-regulated genes markers listed in Table 3, or are products of at least 5 down-regulated genes markers listed in Table
 3. 13. The method of claim 1, wherein each of said gene products is a gene transcript.
 14. The method of claim 13, wherein measurement of each said gene transcript is obtained by a method comprising contacting a positionally-addressable microarray with nucleic acids from said cell sample or nucleic acids derived therefrom under hybridization conditions, and detecting the amount of hybridization that occurs, said microarray comprising one or more polynucleotide probes complementary to a hybridizable sequence of each said gene transcript.
 15. The method of claim 13, wherein measurement of each said gene transcript is obtained by quantitative reverse transcriptase PCR (qRT-PCR).
 16. The method of claim 1, wherein each of said plurality of gene products is a protein. 